International Collaborative Treatment Protocol for Children and Adolescents With Acute Lymphoblastic Leukemia - AIEOP-BFM ALL 2017
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 5,000
- 试验地点
- 114
- 主要终点
- Event-free survival
研究概览
简要总结
The understanding of acute lymphoblastic leukemia (ALL) in childhood and adolescence has largely changed due to extensive genetic research in recent years: ALL is now considered to be a very heterogeneous disease group. The leukemia cells present themselves with quite differently activated regulatory mechanisms of the malignant phenotype. The introduction of more accurate methods of assessing therapy response ("minimal residual disease [MRD] tests") has provided new insights into very different mechanisms of action, including factors influenced by host factors; this has had practical clinical consequences for the use of more individualized therapy. Multimodal therapies have enabled a cure level of over 80% for ALL in this age group. However, the own and international study data show that the therapy toxicity of the contemporary chemotherapy concepts has become unacceptably high, in particular with respect to those intensified therapies used for the treatment of patients at high risk of ALL relapse.
The AIEOP-BFM ALL 2017 study therefore aims for an innovative integrated approach that will not only adapt the risk stratification to new prognostic markers using more comprehensive diagnostics, but above all, qualitatively reorient the therapy. The most important consequence will be that this study is testing immunotherapy with the bispecific antibody blinatumomab as an alternative to particularly intensive and toxic chemotherapy elements in precursor B-cell ALL (pB-ALL) patients with detectable chemotherapy resistance and at high risk of relapse. With the aim to complement the effects of the conventional chemotherapy, Blinatumomab is in addition tested in the large group of pB-ALL patients at intermediate relapse risk with seemingly unremarkable leukemia, but who account for a large proportion of all relapses. Targeted therapy is also used in the form of the proteasome inhibitor bortezomib for patients with pB-ALL and slow response to the drugs of the induction chemotherapy with the aim to overcome intrinsic chemotherapy resistance of the ALL cells. In patients with T-lineage ALL, who have particularly poor chances for cure after relapse, the established consolidation chemotherapy has proved to be particularly effective. This chemotherapy phase is therefore tested in a longer and more intensive form in such T-ALL patients with intermediate or slow early treatment response with the aim to reduce the relapses rate in this subgroup.
详细描述
Patients are stratified into 4 early risk groups for therapy during the consolidation phase (T/early SR, T/early non-SR, pB/early non-HR, pB/early HR) and 5 risk groups for post-consolidation therapy (T/non-HR, T/HR, pB/SR, pB/MR, pB/HR). Risk stratification is based on immunophenotypic lineage, genetics of leukemic cells and treatment response on the basis of cytomorphology and methods for detection minimal residual disease.
The trial includes four randomized study questions testing experimental treatments on top of the risk-stratified standard chemotherapy backbone:
Primary study questions:
Randomization R-eHR: Early High-risk (early HR) pB-ALL defined by genetics and/or inadequate treatment response over the course of induction: Can the probability of event-free survival (pEFS) from time of randomization be improved by additional therapy with the proteasome inhibitor bortezomib during an extended consolidation treatment phase compared with standard extended consolidation?
Randomization R-HR: High-risk (HR) pB-ALL defined by genetics and/or inadequate treatment response by the end of consolidation: Can the pEFS from time of randomization be improved by a treatment concept including two cycles of post-consolidation immunotherapy with blinatumomab (15 µg/m²/d for 28 days per cycle) plus 4 doses intrathecal Methotrexate replacing two conventional highly intensive chemotherapy courses?
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •newly diagnosed acute lymphoblastic leukemia or
- •newly diagnosed mixed phenotype acute leukemia (MPAL) meeting one of the following criteria:
- •biphenotypic with a dominant T or B lineage assignment
- •bilineal either with a dominant lymphoblastic population or if another reasonable rationale exists to treat the patient with an ALL-based therapy regimen
- •newly diagnosed acute undifferentiated leukemia
- •age < 18 years (up to 17 years and 365 days) at the day of diagnosis
- •patient enrolled in a participating center
- •written informed consent to trial participation and transfer and processing of data A subsequent removal from the study is only allowed if the inclusion criteria turn out not to be fulfilled or in the case of pregnancy of the patient.
排除标准
- •Ph+ (BCR-ABL1 or t(9;22)-positive) ALL
- •bilineal leukemia with a lymphoblastic and a separate non-lymphoblastic (≥ 10% of total cells) blast subset
- •pre-treatment with cytostatic drugs
- •glucocorticoid pre-treatment with ≥ 1 mg/kg/d for more than two weeks during the last month before diagnosis
- •treatment started according to another protocol
- •underlying disease that does not allow treatment according to the protocol (e.g. severe congenital heart disease, Charcot-Marie Syndrome, Ataxia-teleangiectasia...)
- •ALL diagnosed as second malignancy and preceding chemotherapy and/or radiotherapy
- •evidence of pregnancy or lactation period
- •Sexually active adolescents not willing to use highly effective contraceptive method (pearl index <1) until 12 months after end of anti-leukemic therapy
- •participation in another clinical trial except for add-on trials within the scope of supportive care approved by the sponsor
- •live vaccine immunization within 2 weeks before start of protocol treatment
研究组 & 干预措施
pB: early (non-)HR-standard/MR-standard
Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX)
Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Cyclophosphamide (Drug)
pB: early (non-)HR-standard/MR-standard
Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX)
Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Cytarabine (Drug)
pB: early (non-)HR-standard/MR-standard
Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX)
Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Daunorubicin (Drug)
pB: early (non-)HR-standard/MR-standard
Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX)
Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Dexamethasone (Drug)
pB: early (non-)HR-standard/MR-standard
Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX)
Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Doxorubicin (Drug)
pB: early (non-)HR-standard/MR-standard
Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX)
Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: 6-Mercaptopurine (Drug)
pB: early (non-)HR-standard/MR-standard
Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX)
Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Methotrexate (Drug)
pB: early (non-)HR-standard/MR-standard
Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX)
Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Pegaspargase (Drug)
pB: early (non-)HR-standard/MR-standard
Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX)
Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Prednisolone (Drug)
pB: early (non-)HR-standard/MR-standard
Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX)
Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Tioguanin (Drug)
pB: early (non-)HR-standard/MR-standard
Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX)
Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Vincristine (Drug)
pB: early (non-)HR-standard/MR-standard
Induction (5 wks): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT methotrexate (MTX)
Consolidation (6 w/4 w): "Consolidation extended" (control arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-mercaptopurine (6-MP), IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 years after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Erwinase (Drug)
pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Bortezomib (Drug)
pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Cyclophosphamide (Drug)
pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Cytarabine (Drug)
pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Daunorubicin (Drug)
pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Dexamethasone (Drug)
pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Doxorubicin (Drug)
pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: 6-Mercaptopurine (Drug)
pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Methotrexate (Drug)
pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Pegaspargase (Drug)
pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Prednisolone (Drug)
pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Tioguanin (Drug)
pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Vincristine (Drug)
pB: early HR-exp./MR-standard
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 wks): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 wks): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX [without preceding blinatumomab (control arm of randomization R-MR)]
Erwinase is given in case of allergy to pegaspargase.
干预措施: Erwinase (Drug)
pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Blinatumomab (Drug)
pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Cyclophosphamide (Drug)
pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Methotrexate (Drug)
pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Cytarabine (Drug)
pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Daunorubicin (Drug)
pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Dexamethasone (Drug)
pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Doxorubicin (Drug)
pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: 6-Mercaptopurine (Drug)
pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Pegaspargase (Drug)
pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Prednisolone (Drug)
pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Tioguanin (Drug)
pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Vincristine (Drug)
pB: early (non)HR-standard/MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Erwinase (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Blinatumomab (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Bortezomib (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Cyclophosphamide (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Cytarabine (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Daunorubicin (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Dexamethasone (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Doxorubicin (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: 6-Mercaptopurine (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Methotrexate (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Pegaspargase (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Prednisolone (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Tioguanin (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Vincristine (Drug)
pB: early HR-exp./MR-exp.
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (given at 1.3 mg/m²/dose on days 50, 53, 56 and 59)
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX,IT MTX
Reinduction (6 weeks): "Protocol II" with dexamethasone, vincristine, doxorubicin, PEG-L-asparaginase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Blinatumomab (4 w): 1 cycle blinatumomab given at 15 µg/m²/day for 28 days (experimental arm of randomization R-MR)
Maintenance phase (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Erwinase (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Cyclophosphamide (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Cytarabine (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Daunorubicin (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Myocet (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Dexamethasone (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Doxorubicin (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Etoposide (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Fludarabine Phosphate (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Ifosfamide (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: 6-Mercaptopurine (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Methotrexate (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Pegaspargase (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Prednisolone (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Tioguanin (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Vincristine (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Vindesine (Drug)
pB: early (non-)HR-standard/HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT methotrexate, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): "Protocol III" given 3 times with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX).
干预措施: Erwinase (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Cyclophosphamide (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Cytarabine (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Daunorubicin (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Myocet (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Dexamethasone (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Doxorubicin (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Etoposide (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Fludarabine Phosphate (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Ifosfamide (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: 6-Mercaptopurine (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Methotrexate (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Pegaspargase (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Prednisolone (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Tioguanin (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Vincristine (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Vindesine (Drug)
pB: early HR-exp./HR-standard
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (3x5 d): Block HR-1' followed by HR-2' and HR-3' (control arm in randomization R-HR) with dexamethasone, vincristine, vindesine, daunorubicin, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, ifosfamide, pegaspargase, etoposide
Reinduction (3x4 w): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Erwinase (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Blinatumomab (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Cyclophosphamide (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Cytarabine (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Daunorubicin (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Myocet (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Dexamethasone (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Doxorubicin (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: 6-Mercaptopurine (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Methotrexate (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Pegaspargase (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Prednisolone (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Tioguanin (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Vincristine (Drug)
pB: early (non-)HR-standard/HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w/4 w): "Consolidation extended" (control arm in randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase or "Consolidation short" (standard arm of early non-HR group) with cyclophosphamide, cytarabine, 6-MP, IT MTX
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after init. diagnosis): 6-MP, MTX
Erwinase is given in case of pegaspargase allergy. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Erwinase (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Blinatumomab (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Cyclophosphamide (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Cytarabine (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Daunorubicin (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Myocet (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Dexamethasone (Drug)
pB: early non-HR/SR
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Cytarabine (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Doxorubicin (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: 6-Mercaptopurine (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Methotrexate (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Pegaspargase (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Prednisolone (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Tioguanin (Drug)
pB: early non-HR/SR
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Daunorubicin (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Vincristine (Drug)
pB: early HR-exp./HR-exp.
Induction (5 w): as in other pB arms
Consolidation (6 w): "Consolidation extended+BZM" (experimental arm of randomization R-eHR) with cyclophosphamide, cytarabine, 6-MP, IT MTX, dexamethasone, vincristine, pegaspargase, bortezomib (1.3 mg/m²/dose on days 50, 53, 56 and 59)
Intensified consolidation (1x5 d + 2x28 d): Block HR-1' with dexamethasone, vincristine, HD-MTX, IT MTX, HD-cytarabine, cyclophosphamide, pegaspargase followed by 2 cycles blinatumomab at 15 µg/m²/day for 28 days per cycle plus 2x2 doses IT MTX (experimental arm of randomization R-HR)
Reinduction (3x4 weeks): as in arm "pB: early (non-)HR-standard/HR-standard" Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Erwinase (Drug)
pB: early non-HR/SR
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Cyclophosphamide (Drug)
pB: early non-HR/SR
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Dexamethasone (Drug)
pB: early non-HR/SR
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Doxorubicin (Drug)
pB: early non-HR/SR
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: 6-Mercaptopurine (Drug)
pB: early non-HR/SR
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Methotrexate (Drug)
pB: early non-HR/SR
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Pegaspargase (Drug)
pB: early non-HR/SR
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Prednisolone (Drug)
pB: early non-HR/SR
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Tioguanin (Drug)
pB: early non-HR/SR
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Vincristine (Drug)
pB: early non-HR/SR
Induction (5 w): "Protocol IA" with prednisolone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Consolidation short" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Erwinase (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Cyclophosphamide (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Cytarabine (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Daunorubicin (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Myocet (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Dexamethasone (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Doxorubicin (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Etoposide (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Fludarabine Phosphate (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Ifosfamide (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: 6-Mercaptopurine (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Methotrexate (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Pegaspargase (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Prednisolone (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Tioguanin (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Vincristine (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Vindesine (Drug)
T: early non-SR-standard/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (4 w): "Protocol IB regular" (control arm in randomization. R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Erwinase (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Cyclophosphamide (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Cytarabine (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Daunorubicin (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Myocet (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Dexamethasone (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Doxorubicin (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Etoposide (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Fludarabine Phosphate (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Ifosfamide (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: 6-Mercaptopurine (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Methotrexate (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Pegaspargase (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Prednisolone (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Tioguanin (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Vincristine (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Vindesine (Drug)
T: early non-SR-exp/(non-)HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX or "Protocol IA-CPM" with prednisolone instead of dexamethasone and additional CPM
Consolidation (6 w): "Protocol IB long" (experimental arm in randomization R-T) with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
non-HR extra-compartment phase and reinduction: as in arm "pB: early non-HR/SR"
HR intensified consolidation and reinduction: as in arm "pB: early (non-)HR-standard/HR-standard"
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase. Pts with poor response to intensified consolidation receive Myocet-FLA (Myocet, fludarabine, HD-cytarabine, IT-MTX)
干预措施: Erwinase (Drug)
T: early SR/non-HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Cyclophosphamide (Drug)
T: early SR/non-HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Cytarabine (Drug)
T: early SR/non-HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Daunorubicin (Drug)
T: early SR/non-HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Dexamethasone (Drug)
T: early SR/non-HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Doxorubicin (Drug)
T: early SR/non-HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: 6-Mercaptopurine (Drug)
T: early SR/non-HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Methotrexate (Drug)
T: early SR/non-HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Pegaspargase (Drug)
T: early SR/non-HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Prednisolone (Drug)
T: early SR/non-HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Tioguanin (Drug)
T: early SR/non-HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Vincristine (Drug)
T: early SR/non-HR
Induction (5 w): "Protocol IA-Dexa" with prednisolone/dexamethasone, vincristine, daunorubicin, pegaspargase, IT MTX
Consolidation (4 w): "Protocol IB regular" with cyclophosphamide, cytarabine, 6-mercaptopurine, IT MTX
Extra-compartment phase (8 w): "Protocol M" with 6-MP, HD-MTX, IT MTX
Reinduction (6 w): "Protocol II" with dexamethasone, vincristine, doxorubicin, pegaspargase, IT MTX, cyclophosphamide, tioguanine, cytarabine
Maintenance (until 2 yrs after initial diagnosis): 6-MP, MTX
Erwinase is given in case of allergy to pegaspargase.
干预措施: Erwinase (Drug)
结局指标
主要结局
Event-free survival
时间窗: Assessed up to 120 months from start of study
Randomization R-eHR, R-HR and R-T: Time from randomization until the first event defined as follow: cytomorphological or molecular non-response (resistance to protocol treatment, considered as event at day zero), relapse, second malignancy or death from any cause. This will be called EFS time.
Disease-free survival
时间窗: Assessed up to 120 months from start of study
Randomization R-MR: Time from randomization until the first event defined as follow: Relapse, second malignancy or death from any cause. This will be called DFS time.
次要结局
- Survival(Assessed up to 120 months from start of study)
- Treatment-related mortality(Assessed up to 120 months from start of study)
- Adverse Events of interest/Serious Adverse Events(Assessed up to 120 months from start of study)
- MRD response(Measurements of MRD response at end of randomized treatments (intended time frame 13 weeks in R-eHR/R-T, 26 weeks in R-HR, 34 weeks in R-MR).)
- Proportion of patients with Blina Poor-Response(Measurements of MRD response intended after 30 weeks from individual start of treatment, assessment of proportion at 120 months from start of study)
研究者
Martin Schrappe
Professor MD, FRCP (Glasg), Chair of Pediatrics I
University Hospital Schleswig-Holstein