A Phase III Randomized Trial for Newly Diagnosed High Risk B-Lymphoblastic Leukemia (B-ALL) Including a Stratum Evaluating Dasatinib (NSC#732517) in Patients With Ph-like Tyrosine Kinase Inhibitor (TKI) Sensitive Mutations
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 5,949
- 试验地点
- 478
- 主要终点
- DFS of Non-DS HR Post-induction Patients Receiving Intrathecal (IT) Methotrexate (MTX) Compared With Patients Receiving Intrathecal Triple Therapy (ITT) on a Modified Berlin-Frankfurt-Munster (MBFM) Interim Maintenance High-dose Methotrexate Backbone
研究概览
简要总结
This randomized phase III trial studies how well combination chemotherapy works in treating young patients with newly diagnosed B acute lymphoblastic leukemia that is likely to come back or spread, and in patients with Philadelphia chromosome (Ph)-like tyrosine kinase inhibitor (TKI) sensitive mutations. Chemotherapy drugs, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine if the administration of post-Induction age-adjusted intrathecal triple therapy (ITT) on a Modified Berlin-Frankfurt-Munster (MBFM) interim maintenance high-dose methotrexate (IMHDM) backbone will improve 5-year disease-free survival (DFS) of children with high-risk (HR) B-acute lymphoblastic leukemia (ALL) compared to age-adjusted intrathecal (IT) methotrexate (MTX). (Completed effective March 19, 2018) II. To determine, in a randomized fashion, if the cyclophosphamide + etoposide containing regimen (Experimental Arm 1) will improve the 4-year DFS of children, adolescents, and young adults with very high-risk (VHR) B-ALL compared to a modified MBFM-IMHDM regimen that contains a second IM (Control Arm). (Completed effective February 15, 2017)
SECONDARY OBJECTIVES:
I. To determine the toxicity and tolerability of post-Induction age-adjusted ITT compared to age-adjusted IT MTX in children with HR B-ALL. (Completed effective March 19, 2018) II. To determine the toxicity and tolerability of Experimental Arm 1 compared to the Control Arm in children, adolescents, and young adults with VHR B-ALL. (Completed effective February 15, 2017) III. To determine whether a single-arm, modified Induction with limited anthracycline exposure and post-Induction therapy regimen with MBFM-interim maintenance intermediate dose methotrexate (IMIDM) and reduced vincristine (vincristine sulfate)/steroid pulse frequency and enhanced supportive care in children with Down syndrome (DS) and HR B-ALL will result in a >= 65% 5-year DFS and < 10% Induction mortality.
IV. To describe the outcomes for children and young adults with Philadelphia chromosome (Ph)-like B-ALL and a predicted TKI-sensitive mutation treated with dasatinib plus MBFM-IMHDM.
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
- None
入排标准
- 年龄范围
- 1 Year 至 31 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must be enrolled on APEC14B1 and consented to Eligibility Screening on the Part A consent form prior to enrollment on AALL1131
- •White Blood Cell Count (WBC) Criteria
- •Age 1-9.99 years: WBC >= 50 000/uL
- •Age 10-30.99 years: Any WBC
- •Age 1-30.99 years: Any WBC with:
- •Testicular leukemia
- •CNS leukemia (CNS3)
- •Steroid pretreatment
- •Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health Organization [WHO] classification) (also termed B-precursor acute lymphoblastic leukemia); patients with Down syndrome are also eligible
- •Organ function requirements for patients with Ph-like ALL and a predicted TKI-sensitive mutation: patients identified as Ph-like with a TKI-sensitive kinase mutation must have assessment of organ function performed within 3 days of study entry onto the dasatinib arm of AALL1131
- •Creatinine clearance or radioisotope glomerular filtration rate (GFR) > 70mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:
- •Age: Maximum Serum Creatinine (mg/dL)
- •1 to < 6 months: 0.4 (male) 0.4 (female)
- •6 months to < 1 year: 0.5 (male) 0.5 (female)
- •1 to < 2 years: 0.6 (male) 0.6 (female)
- •2 < 6 years: 0.8 (male) 0.8 (female)
- •6 to < 10 years: 1.0 (male) 1.0 (female)
- •10 to < 13 years: 1.2 (male) 1.2 (female)
- •13 to < 16 years: 1.5 (male) 1.4 (female)
- •> 16 years: 1.7 (male) 1.4 (female)
- •Direct bilirubin =< 3 x upper limit of normal (ULN) for age, and
- •Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 10 x upper limit of normal (ULN) for age
- •Shortening fraction >= 27% by echocardiogram, or ejection fraction >= 50% by gated radionuclide study
- •Patients must have an electrocardiogram (EKG) fewer than 6 days prior to enrollment on the dasatinib arm; patients who have had cardiac assessments by echocardiogram or radionuclide scan at the beginning of induction do not need to have these repeated prior to study entry; correct QT interval (QTc) < 450 msec on baseline electrocardiogram as measured by the Friderica or Bazett formula
- •No major conduction abnormality (unless a cardiac pacemaker is present)
- •No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% at sea level if there is clinical indication for determination
- •Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled; however, drugs that induce CYP3A4/5 (carbamazepine, oxcarbazepine, phenytoin, primidone, phenobarbital) should be avoided
- •Eligibility criteria for the Longitudinal, Computerized Assessment of Neurocognitive Functioning study
- •Patients must be aged 6 to 13 years at time of B-ALL diagnosis, enrolled on AALL1131
- •Patients must be English-, French- or Spanish-speaking (languages in which the assessment is available)
- •Patients must have no known history of neurodevelopmental disorder prior to diagnosis of B-ALL (e.g., Down syndrome, Fragile X, William's Syndrome, mental retardation)
- •Patients must have no significant visual impairment that would prevent computer use and recognition of the visual test stimuli
- •Eligibility criteria for the National Cancer Institute (NCI) standard risk patients from AALL0932 enrolling on this study at the end of Induction
- •Effective March 19, 2018, patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 or the HR B-ALL stratum of this study at the end of Induction:
- •Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day 8 peripheral blood (PB) minimal residual disease (MRD) >= 1% and day 29 bone marrow (BM) MRD < 0.01%
- •With favorable cytogenetics (ETV6-RUNX1 or double trisomies 4+10), with any day 8 PB MRD and day 29 BM MRD >= 0.01%
- •Both NCI standard risk (SR) and HR patients without Down syndrome and with testicular disease at diagnosis, who do not meet other VHR criteria
- •Effective Amendment 6, patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 or the VHR stratum of AALL1131:
- •Intrachromosomal amplification of chromosome 21 (iAMP21)
- •Mixed-lineage leukemia (MLL) rearrangement
- •Hypodiploidy (n < 44 chromosomes and/or a deoxyribonucleic acid [DNA] index < 0.81)
- •Induction failure (M3 BM at day 29)
- •Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day 29 BM MRD >= 0.01%
- •Patients enrolled on AALL0932, with Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the DS HR B-ALL stratum of this study at the end of Induction:
- •Day 29 MRD >= 0.01%
- •MLL rearrangement
- •Hypodiploidy (n < 45 chromosomes and/or DNA index < 0.81)
- •DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction failure (M3 BM day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for post-Induction therapy on either trial (AALL0932 or AALL1131)
- •All patients and/or their parents or legal guardians must sign a written informed consent
- •All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met
排除标准
- •With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation of protocol therapy on AALL1131; patients cannot have secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy; patients receiving prior steroid therapy may be eligible for AALL1131
- •Patients with BCR-ABL1 fusion are not eligible for post-induction therapy on this study but may be eligible to enroll in a successor Children's Oncology Group (COG) Philadelphia positive (Ph+) ALL trial by day 15 Induction
- •DS HR B-ALL patients with Induction failure or BCR-ABL1
- •Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs
- •Lactating females are not eligible unless they have agreed not to breastfeed their infant
- •Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
- •Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation
研究组 & 干预措施
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Laboratory Biomarker Analysis (Other)
DS HR B-ALL (RER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Leucovorin Calcium (Drug)
DS HR B-ALL (RER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Mercaptopurine (Drug)
DS HR B-ALL (RER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Vincristine Sulfate (Drug)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Cyclophosphamide (Drug)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Dexamethasone (Drug)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Doxorubicin Hydrochloride (Drug)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Mercaptopurine (Drug)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Vincristine Sulfate (Drug)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Radiation Therapy (Radiation)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Pegaspargase (Drug)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Methotrexate (Drug)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Prednisone (Drug)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Vincristine Sulfate (Drug)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Doxorubicin Hydrochloride (Drug)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Dexamethasone (Drug)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Radiation Therapy (Radiation)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Vincristine Sulfate (Drug)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Prednisone (Drug)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Pegaspargase (Drug)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Laboratory Biomarker Analysis (Other)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Mercaptopurine (Drug)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Methotrexate (Drug)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Etoposide (Drug)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Radiation Therapy (Radiation)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Thioguanine (Drug)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Vincristine Sulfate (Drug)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Mercaptopurine (Drug)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Radiation Therapy (Radiation)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Leucovorin Calcium (Drug)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Pegaspargase (Drug)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Vincristine Sulfate (Drug)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Cyclophosphamide (Drug)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Cytarabine (Drug)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Mercaptopurine (Drug)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Vincristine Sulfate (Drug)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Leucovorin Calcium (Drug)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Methotrexate (Drug)
Group III PH-like predicted TKI-sensitive kinase mutation
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Leucovorin Calcium (Drug)
Group III PH-like predicted TKI-sensitive kinase mutation
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Mercaptopurine (Drug)
Group III PH-like predicted TKI-sensitive kinase mutation
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Methotrexate (Drug)
Group III PH-like predicted TKI-sensitive kinase mutation
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Vincristine Sulfate (Drug)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Pegaspargase (Drug)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Thioguanine (Drug)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Cytarabine (Drug)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Cytarabine (Drug)
Group III PH-like predicted TKI-sensitive kinase mutation
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Prednisone (Drug)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Prednisone (Drug)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Clofarabine (Drug)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Thioguanine (Drug)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Methotrexate (Drug)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Cyclophosphamide (Drug)
DS HR B-ALL (RER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Cyclophosphamide (Drug)
DS HR B-ALL (RER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Cytarabine (Drug)
DS HR B-ALL (RER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Radiation Therapy (Radiation)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Cyclophosphamide (Drug)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Laboratory Biomarker Analysis (Other)
Group III PH-like predicted TKI-sensitive kinase mutation
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Laboratory Biomarker Analysis (Other)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Daunorubicin Hydrochloride (Drug)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Daunorubicin Hydrochloride (Drug)
DS HR B-ALL (RER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Laboratory Biomarker Analysis (Other)
Group III PH-like predicted TKI-sensitive kinase mutation
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Cytarabine (Drug)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Laboratory Biomarker Analysis (Other)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Radiation Therapy (Radiation)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Laboratory Biomarker Analysis (Other)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Laboratory Biomarker Analysis (Other)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Radiation Therapy (Radiation)
DS HR B-ALL (RER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Doxorubicin Hydrochloride (Drug)
DS HR B-ALL (RER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Pegaspargase (Drug)
Group III PH-like predicted TKI-sensitive kinase mutation
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Doxorubicin Hydrochloride (Drug)
DS HR B-ALL (RER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Thioguanine (Drug)
DS HR B-ALL (RER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Methotrexate (Drug)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Hydrocortisone Sodium Succinate (Drug)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Cytarabine (Drug)
Group III PH-like predicted TKI-sensitive kinase mutation
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Dasatinib (Drug)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Prednisone (Drug)
DS HR B-ALL (RER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Dexamethasone (Drug)
DS HR B-ALL (RER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Prednisone (Drug)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Leucovorin Calcium (Drug)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Methotrexate (Drug)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Pegaspargase (Drug)
DS HR B-ALL (SER)
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Thioguanine (Drug)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Cyclophosphamide (Drug)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Dexamethasone (Drug)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Doxorubicin Hydrochloride (Drug)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Leucovorin Calcium (Drug)
Group I Arm A (HR B-ALL)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Mercaptopurine (Drug)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Daunorubicin Hydrochloride (Drug)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Leucovorin Calcium (Drug)
Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Mercaptopurine (Drug)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Cytarabine (Drug)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Daunorubicin Hydrochloride (Drug)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Dexamethasone (Drug)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Doxorubicin Hydrochloride (Drug)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Leucovorin Calcium (Drug)
Group II Arm A (VHR B-ALL - Control Arm)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Pegaspargase (Drug)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Cyclophosphamide (Drug)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Cytarabine (Drug)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Daunorubicin Hydrochloride (Drug)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Doxorubicin Hydrochloride (Drug)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Methotrexate (Drug)
Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)
Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Prednisone (Drug)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Daunorubicin Hydrochloride (Drug)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Dexamethasone (Drug)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Doxorubicin Hydrochloride (Drug)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Etoposide (Drug)
Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)
Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.
See outline for details.
干预措施: Prednisone (Drug)
Group III PH-like predicted TKI-sensitive kinase mutation
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Cyclophosphamide (Drug)
Group III PH-like predicted TKI-sensitive kinase mutation
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Daunorubicin Hydrochloride (Drug)
Group III PH-like predicted TKI-sensitive kinase mutation
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Dexamethasone (Drug)
Group III PH-like predicted TKI-sensitive kinase mutation
Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.
See outline for details.
干预措施: Pegaspargase (Drug)
结局指标
主要结局
DFS of Non-DS HR Post-induction Patients Receiving Intrathecal (IT) Methotrexate (MTX) Compared With Patients Receiving Intrathecal Triple Therapy (ITT) on a Modified Berlin-Frankfurt-Munster (MBFM) Interim Maintenance High-dose Methotrexate Backbone
时间窗: At 5 years
DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. Compared using 2-sided log rank test, alpha = 5%. (Completed effective March 19, 2018)
DFS of Non-DS VHR Post-Induction Patients Who Receive a Modified MBFM-IMHDM Regimen That Contains a Second IM (Control Arm) Compared to Patients Receive the Cyclophosphamide + Etoposide Containing Regimen (Experimental Arm 1)
时间窗: At 4 years
(Completed effective February 15, 2017) DFS time is defined as time from randomization end of induction to first event (relapse, second malignant neoplasm, death) or date of last contact for patients who are event-free. Compared using a 1-sided log rank test, alpha of 2.5%.
次要结局
- The Prevalence of Cognitive Deficits Measured by CogState (Domain: Working Memory), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy(Up to 10 years)
- Incidence of Osteonecrosis (ON) Defined by Magnetic Resonance (MR) Imaging in Children, Adolescents, and Young Adults 10 Years of Age and Greater(Up to 10 years)
- The Prevalence of Cognitive Deficits Measured by CogState (Domain: Processing Speed), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy(Up to 10 years)
- The Prevalence of Cognitive Deficits Measured by CogState (Domain: Visual Attention), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy(Up to 10 years)
- Toxicity and Tolerability of Post-induction Age-adjusted ITT Compared to Age-adjusted IT MTX in Children With HR B-ALL(Up to 10 years)
- Induction Mortality in Patients With DS and HR B-ALL Treated With Modified Induction(At 1 month)
- 5-year DFS in Patients With Down Syndrome (DS) and HR B-ALL Treated With Modified Induction and Post-Induction Therapy Regimen With MBFM-IMIDM(At 5 years)
- DFS for Children and Young Adults With Ph-like B-ALL and a Predicted Tyrosine Kinase Inhibitor (TKI)-Sensitive Mutation Treated With Dasatinib Plus MBFM-IMHDM(Up to 4 years)
- Overall Survival (OS) Rate for VHR B-ALL Patients, Overall and by Randomized Arm.(At 4 years)
- The Prevalence of Cognitive Deficits Measured by CogState (Domain: Executive Function), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy(Up to 10 years)
- The Prevalence of Cognitive Deficits Measured by CogState (Domain: Visual Learning), in Children (Ages 6 to < 13 Years) With HR- and VHR B-ALL at 1 Year Off Therapy(Up to 10 years)
- Toxicity and Tolerability of Experimental Arm 1 and Control Arm in Patients With VHR B-ALL(Up to 10 years)
- Toxicity and Tolerability of MBFM-interim Maintenance Intermediate Dose Methotrexate (IMIDM) in Children With Down Syndrome(Up to 10 years)
- Overall Survival (OS) Rate for HR B-ALL Patients, Overall and by Randomized Arm(At 5 years)