Total Therapy XVII for Newly Diagnosed Patients With Acute Lymphoblastic Leukemia and Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 790
- 试验地点
- 16
- 主要终点
- Event-free survival of ALL patients (EFS)
研究概览
简要总结
The overarching objective of this study is to use novel precision medicine strategies based on inherited and acquired leukemia-specific genomic features and targeted treatment approaches to improve the cure rate and quality of life of children with acute lymphoblastic leukemia (ALL) and acute lymphoblastic lymphoma (LLy).
Primary Therapeutic Objectives:
- To improve the event-free survival of provisional standard- or high-risk patients with genetically or immunologically targetable lesions or minimal residual disease (MRD) ≥ 5% at Day 15 or Day 22 or ≥1% at the end of Remission Induction, by the addition of molecular and immunotherapeutic approaches including tyrosine kinase inhibitors or chimeric antigen receptor (CAR) T cell / blinatumomab for refractory B-acute lymphoblastic leukemia (B-ALL) or B-lymphoblastic lymphoma (B-LLy), and the proteasome inhibitor bortezomib for those lacking targetable lesions.
- To improve overall treatment outcome of T acute lymphoblastic leukemia (T-ALL) and T-lymphoblastic lymphoma (T-LLy) by optimizing pegaspargase and cyclophosphamide treatment and by the addition of new agents in patients with targetable genomic abnormalities (e.g., activated tyrosine kinases or JAK/STAT mutations) or by the addition of bortezomib for those who have a poor early response to treatment but no targetable lesions, and by administering nelarabine to T-ALL and T-LLy patients with leukemia/lymphoma cells in cerebrospinal fluid at diagnosis or MRD ≥0.01% at the end of induction.
- To determine in a randomized study design whether the incidence and/or severity of acute vincristine-induced peripheral neuropathy can be reduced by decreasing the dosage of vincristine in patients with the high-risk CEP72 TT genotype or by shortening the duration of vincristine therapy in standard/high-risk patients with the CEP72 CC or CT genotype.
Secondary Therapeutic Objectives:
- To estimate the event-free survival and overall survival of children with ALL and to assess the non-inferiority of TOTXVII compared to the historical control given by TOTXVI.
- To estimate the event-free survival and overall survival of children with LLy when ALL diagnostic and treatment approaches are used.
- To evaluate the efficacy of blinatumomab in B-ALL patients with end of induction MRD ≥0.01% to <1% and those (regardless of MRD level or TOTXVII risk category) with the genetic subtypes of BCR-ABL1, ABL-class fusion, JAK-STAT activating mutation, hypodiploid, iAMP21, ETV6-RUNX1-like, MEF2D, TCF3-HLF, or BCL2/MYC or with Down syndrome, by comparing event-free survival to historical control from TOTXVI.
- To determine the tolerability of combination therapy with ruxolitinib and Early Intensification therapy in patients with activation of JAK-STAT signaling that can be inhibited by ruxolitinib and Day 15 or Day 22 MRD ≥5%, Day 42 MRD ≥1%, or LLy patients without complete response at the End of Induction and all patients with early T cell precursor leukemia.
Biological Objectives:
- To use data from clinical genomic sequencing of diagnosis, germline/remission and MRD samples to guide therapy, including incorporation of targeted agents and institution of genetic counseling and cancer surveillance.
- To evaluate and implement deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) sequencing-based methods to monitor levels of MRD in bone marrow, blood, and cerebrospinal fluid.
- To assess clonal diversity and evolution of pre-leukemic and leukemic populations using DNA variant detection and single-cell genomic analyses in a non-clinical, research setting.
- To identify germline or somatic genomic variants associated with drug resistance of ALL cells to conventional and newer targeted anti-leukemic agents in a non-clinical, research setting.
- To compare drug sensitivity of ALL cells from diagnosis to relapse in vitro and in vivo and determine if acquired resistance to specific agents is related to specific somatic genome variants that are not detected or found in only a minor clone at initial diagnosis.
Supportive Care Objectives
- To conduct serial neurocognitive monitoring of patients to investigate the neurocognitive trajectory, mechanisms, and risk factors.
- To evaluate the impact of low-magnitude high frequency mechanical stimulation on bone mineral density and markers of bone turnover.
There are several Exploratory Objectives.
详细描述
Participants will be classified into one of three categories (low-, standard-, or high-risk) based on the presenting age, leukocyte count/lymphoma staging, presence or absence of CNS-3 status or testicular disease, immunophenotype, molecular genetics, DNA index, and early response to therapy.
Treatment will consist of three main phases: Remission Induction, Consolidation, and Continuation. Early Intensification therapy will be given prior to Consolidation to patients with provisional standard-risk or high-risk ALL/LLy or any provisional low-risk patients with Day 15 MRD ≥1% as well as provisional low-risk LLy patients who do not obtain complete response at the end of Induction. Patients with mixed phenotype acute leukemia (MPAL) are treated by using the same treatment stratification used in ALL although analysis is performed separately from ALL or LLy cohorts.
Brief outline of treatment plan:
Patients will be assigned to treatment based on risk group: Low-Risk, Standard-Risk and High-Risk and cell type (T or B cell).
Remission Induction initially consists of prednisone (28 days), vincristine (4 weekly doses), daunorubicin (1 to 3 weekly doses), and pegaspargase 1 dose for all patients and 2 doses for those with Day 15 MRD 1% or higher. The second part (given over 2 weeks and overlapping with the last week of the first part of induction) consists of cyclophosphamide, cytarabine, and mercaptopurine combinations. Dasatinib will be added for patients with Ph+ and Ph-like ABL-class fusions and bortezomib will be given to patients with no targetable lesions and Day 15 or Day 22 minimal residual disease (MRD) ≥ 5% on Days 29 and 32.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
Only certain outcome measures as indicated will be blinded to the outcomes assessor.
入排标准
- 年龄范围
- 1 Year 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of B- or T-ALL or LLy by immunophenotyping:
- •LLy participants must have < 25% tumor cells in bone marrow and peripheral blood by morphology and flow cytometry. If any of these show ≥25% blasts, patient will be considered to have leukemia. Patients with MPAL are eligible.
- •Age 1-18 years (inclusive).
- •No prior therapy, or limited prior therapy, including systemic glucocorticoids for one week or less, one dose of vincristine, emergency radiation therapy (e.g., to the mediastinum, head and neck, orbit, etc.) and one dose of intrathecal chemotherapy.
- •Written, informed consent and assent following Institutional Review Board (IRB), National Cancer Institute (NCI), Food and Drug Administration (FDA), and Office of Human Research Protections (OHRP) Guidelines.
排除标准
- •Participants who are pregnant or lactating. Males or females of reproductive potential must agree to use effective contraception for the duration of study participation.
- •Inability or unwillingness of research participant or legal guardian/representative to give written informed consent.
研究组 & 干预措施
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Pegaspargase (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Asparaginase Erwinia chrysanthemi (recombinant)-rywn (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Vincristine (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Dasatinib (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Erwinase® (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Erwinase® (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Erwinase® (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Erwinase® (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Cytarabine (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Bortezomib (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Doxorubicin (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Daunorubicin (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Clofarabine (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Erwinase® (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Prednisone (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Vincristine (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Daunorubicin (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Cytarabine (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Cyclophosphamide (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Mercaptopurine (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Methotrexate (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Dasatinib (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Blinatumomab (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Dexamethasone (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Thioguanine (Drug)
B-ALL and B-LLy, Low-risk
Patients with low-risk B ALL and LLy will have Induction (6 weeks), Consolidation (8 weeks), and Continuation (120 weeks). During Remission Induction therapy, prednisone dose is 40mg/m^2 and 1-2 doses of daunorubicin (based on day 8 peripheral blood MRD in patients with ETV6-RUNX1 or hyperdiploid) are given. Dasatinib is given for patients with ABL-class fusion. Blinatumomab will be given to patients with certain genetic subtypes and those with Down syndrome.
Interventions: Prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, thioguanine, methotrexate, dexamethasone, blinatumomab.
干预措施: Calaspargase Pegol (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Prednisone (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Daunorubicin (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Pegaspargase (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Cyclophosphamide (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Mercaptopurine (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Methotrexate (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Blinatumomab (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Ruxolitinib (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Dexamethasone (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Thioguanine (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Asparaginase Erwinia chrysanthemi (recombinant)-rywn (Drug)
B-ALL and B-LLy, Standard-risk
Induction (6wks), Early Intensification (4wks), Consolidation (8wks) and Continuation (120 wks). Remission Induction: Prednisone dose is 40mg/m^2 and 2 doses daunorubicin are given. Dasatinib: given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib: given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5%, LLy patients who don't qualify for complete response at end of Remission Induction and all patients with ETP and T/M MPAL. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD >5%. Blinatumomab will be given to patients with residual disease at the end of induction (≥0.01% and <1%), certain genetic subtypes and Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, thioguanine, methotrexate, dexamethasone, doxorubicin
干预措施: Calaspargase Pegol (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Prednisone (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Vincristine (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Pegaspargase (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Cyclophosphamide (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Cytarabine (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Mercaptopurine (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Dasatinib (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Methotrexate (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Blinatumomab (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Ruxolitinib (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Bortezomib (Drug)
ALL, CEP72 T/T, Vincristine
Patients with the CEP72 rs904627T/T genotype (~16% of patients) will be randomized (unblinded design, only those who evaluate neuropathy are blinded) to receive either 1.5 mg/m^2 or 1 mg/m^2 of vincristine after Continuation Week 1. Patients in low- risk will complete vincristine in Week 49 and those in standard/high-risk will complete in Week 101.
Intervention: vincristine.
干预措施: Vincristine (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Etoposide (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Dexamethasone (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Clofarabine (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Thioguanine (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Vincristine (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Asparaginase Erwinia chrysanthemi (recombinant)-rywn (Drug)
B-ALL and B-LLy, High-risk
Induction (6 weeks), Early Intensification (4 weeks), Consolidation (8 weeks), and Immunotherapy (chimeric antigen receptor [CAR] T cells). Patients who do not respond to Immunotherapy will receive Reintensification therapy. During Remission Induction therapy, prednisone dose is 40mg/m^2 and 2 doses of daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib are given as done for patients with standard-risk B-ALL but are discontinued in Immunotherapy and Reintensification therapy. Blinatumomab will be given to patients who are not able to receive CAR T cell therapy and patients with certain genetic subtypes and those with Down syndrome.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, blinatumomab, etoposide, dexamethasone, clofarabine, thioguanine, methotrexate.
干预措施: Calaspargase Pegol (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Prednisone (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Daunorubicin (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Pegaspargase (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Mercaptopurine (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Cyclophosphamide (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Cytarabine (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Dasatinib (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Methotrexate (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Ruxolitinib (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Doxorubicin (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Dexamethasone (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Bortezomib (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Bortezomib (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Nelarabine (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Thioguanine (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Prednisone (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Asparaginase Erwinia chrysanthemi (recombinant)-rywn (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Daunorubicin (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Ruxolitinib (Drug)
T-ALL and T-LLy, Standard-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Continuation (120 wks). During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib is given for patients with Ph+ and those with ABL-class fusion. Ruxolitinib is given for patients with activation of JAK-STAT signaling; ALL patients with Day 15 or Day 22 MRD ≥5% and all patients with ETP and T/M MPAL and LLy patients who don't qualify for complete response at end of Remission Induction. Bortezomib is given to patients without targetable lesions and Day 15 or Day 22 MRD ≥ 5%.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, dexamethasone, doxorubicin, nelarabine, thioguanine.
干预措施: Calaspargase Pegol (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Vincristine (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Cytarabine (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Pegaspargase (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Cyclophosphamide (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Methotrexate (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Mercaptopurine (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Dasatinib (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Dexamethasone (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Etoposide (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Vorinostat (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Idarubicin (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Nelarabine (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Thioguanine (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Asparaginase Erwinia chrysanthemi (recombinant)-rywn (Drug)
T-ALL and T-LLy, High-risk
Induction (6 wks), Early Intensification (4 wks), Consolidation (8 wks), and Reintensification. During Remission Induction therapy, prednisone dose is 60mg/m^2 and 3 doses daunorubicin are given. Dasatinib, ruxolitinib, and bortezomib given as done for patients with standard-risk T-ALL but are discontinued in Reintensification therapy.
Interventions: prednisone, vincristine, daunorubicin, pegaspargase (or Erwinase®, Rylaze™ or Calaspargase pegol), cyclophosphamide, cytarabine, mercaptopurine, dasatinib, bortezomib, ruxolitinib, methotrexate, etoposide, dexamethasone, clofarabine, vorinostat, idarubicin, nelarabine, thioguanine..
干预措施: Calaspargase Pegol (Drug)
ALL, CEP72 C/T or C/C, Vincristine
Patients with either a CEP72 rs904627 C/T or C/C genotype (~84% of patients) will be randomized (unblinded design, only those who evaluate neuropathy are blinded) to receive vincristine (2 mg/m^2 per dose except during Reinduction I and Reinduction II when 3 weekly doses of 1.5 mg/m^2 will be given) and dexamethasone pulses through Week 49 of Continuation Treatment or through Week 101 of Continuation Treatment. Patients at low-risk will complete vincristine in Week 49.
Interventions: vincristine, dexamethasone, methotrexate, mercaptopurine.
干预措施: Vincristine (Drug)
ALL, CEP72 C/T or C/C, Vincristine
Patients with either a CEP72 rs904627 C/T or C/C genotype (~84% of patients) will be randomized (unblinded design, only those who evaluate neuropathy are blinded) to receive vincristine (2 mg/m^2 per dose except during Reinduction I and Reinduction II when 3 weekly doses of 1.5 mg/m^2 will be given) and dexamethasone pulses through Week 49 of Continuation Treatment or through Week 101 of Continuation Treatment. Patients at low-risk will complete vincristine in Week 49.
Interventions: vincristine, dexamethasone, methotrexate, mercaptopurine.
干预措施: Mercaptopurine (Drug)
ALL, CEP72 C/T or C/C, Vincristine
Patients with either a CEP72 rs904627 C/T or C/C genotype (~84% of patients) will be randomized (unblinded design, only those who evaluate neuropathy are blinded) to receive vincristine (2 mg/m^2 per dose except during Reinduction I and Reinduction II when 3 weekly doses of 1.5 mg/m^2 will be given) and dexamethasone pulses through Week 49 of Continuation Treatment or through Week 101 of Continuation Treatment. Patients at low-risk will complete vincristine in Week 49.
Interventions: vincristine, dexamethasone, methotrexate, mercaptopurine.
干预措施: Methotrexate (Drug)
ALL, CEP72 C/T or C/C, Vincristine
Patients with either a CEP72 rs904627 C/T or C/C genotype (~84% of patients) will be randomized (unblinded design, only those who evaluate neuropathy are blinded) to receive vincristine (2 mg/m^2 per dose except during Reinduction I and Reinduction II when 3 weekly doses of 1.5 mg/m^2 will be given) and dexamethasone pulses through Week 49 of Continuation Treatment or through Week 101 of Continuation Treatment. Patients at low-risk will complete vincristine in Week 49.
Interventions: vincristine, dexamethasone, methotrexate, mercaptopurine.
干预措施: Dexamethasone (Drug)
结局指标
主要结局
Event-free survival of ALL patients (EFS)
时间窗: At 3.5 years after enrollment of the last participant
5-year EFS: Kaplan-Meier estimates of EFS curve of ALL patients will be computed and compared historically with those of the St. Jude Children's Research Hospital's (SJCRH) TOTXVI study (NCT00549848). All eligible patients entered on the current TOT17 study will be included in these comparisons. Comparisons by log-rank tests will be made both un-stratified and stratified by risk groups.
Proportion of patients with CEP72TT genotype who develop two or more episodes of Grade 2 or higher neuropathy during Continuation
时间窗: At 6 months after the last randomized patient completes Continuation Treatment (Week 120).
This will be a single-blind, stratified block randomized experiment. Although the investigators who evaluate neuropathy and neuropathic pain and the patients are blinded for treatment assignment, treating clinicians and pharmacy staff are not. Patients will be randomized at a 1:1 ratio into two treatment groups: 1.5 mg/m\^2 vs. 1 mg/m\^2 vincristine (VCR) dose. Randomization will be stratified by two factors known to significantly affect neuropathy during the Continuation phase, namely, Grade 2 or higher neuropathy prior to Continuation (none, 1 episode, 2 or more episodes) and race (black, others). The proportion of patients who develop two or more episodes of Grade 2 or higher neuropathy during Continuation Treatment will be compared between the two VCR dose groups, using a Z-test for two sample proportions.
Cumulative incidence of Grade 2 or higher neuropathy in patients with CEP72 CC or CT genotype
时间窗: After the last randomized patient is followed for 1 year after Week 101 of Continuation therapy
This will be a single blind stratified block randomized experiment. The investigators who evaluate neuropathy and neuropathic pain and the patients are blinded for treatment assignment. Treating clinicians and pharmacy staff will not be blinded. Standard/high-risk patients will be randomized at a 1:1 ratio into two treatment groups at Week 49 of Continuation therapy: to vincristine + dexamethasone (VCR+DEX) pulses or to 6-mercaptopurine + methotrexate (6MP+MTX). The primary analysis will compare the cumulative incidence of the first episode of Grade 2 or higher neuropathy or neuropathic pain (the end point) by stratified Gray's test. Adverse events other than the endpoint rendering a patient drop out after Continuation Week 49 are regarded as competing events.
次要结局
- EFS of LLy patients(3.5 years after enrollment of the last patient)
- 5-year OS of LLy patients(3.5 years after enrollment of the last patient)
- The efficacy of blinatumomab in B-ALL patients(3.5 years after enrollment of the last patient)
- Isolated CNS relapse in CNS1b patients(3.5 years after enrollment of the last patient)
- Comparison of drug sensitivity of ALL cells between diagnosis and relapse in vitro and in vivo(5 years after enrollment of the last participant)
- Change in bone mineral density (BMD) in the tibia(From baseline to week 49 Continuation treatment (up to 6 months after last patient completes week 49 Continuation))
- 5-year overall survival (OS) of ALL patients compared to historical controls(3.5 years after enrollment of the last patient)
- Comparison of MRD measurements between flow cytometry and sequencing(From Day 8 through Day 42 after remission induction (At 6 months after enrollment of the 40^t^h evaluable patient))
- Log hazard ratio of the association of low level of MRD and treatment outcome(3.5 years after enrollment of the last patient)
- Comparison of bone marrow and peripheral blood MRD(From Day 15 through Day 42 of remission induction and end of therapy (At 6 months after enrollment of the last evaluable patient))
- Level of clonal diversity and rise of leukemic clones during treatment(From Day 1 through week 120 of continuation (at 6 months after the last enrolled patient completes Week 120))
- Change in markers of bone turnover(From baseline to week 49 Continuation treatment (up to 6 months after last patient completes week 49 Continuation))
- Number and type of germline or somatic genomic variants associated with drug resistance(3.5 years after enrollment of the last participant)