Treatment of Patients With Newly Diagnosed Standard Risk B-Lymphoblastic Leukemia (B-ALL) or Localized B-Lineage Lymphoblastic Lymphoma (B-LLy)
Overview
- Phase
- Phase 3
- Intervention
- Dexamethasone
- Conditions
- Acute Lymphoblastic Leukemia
- Sponsor
- Children's Oncology Group
- Enrollment
- 9350
- Locations
- 243
- Primary Endpoint
- DFS for SR Down Syndrome Patients With Standardized Treatment and Enhanced Supportive Care
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
This partially randomized phase III trial studies the side effects of different combinations of risk-adapted chemotherapy regimens and how well they work in treating younger patients with newly diagnosed standard-risk acute lymphoblastic leukemia or B-lineage lymphoblastic lymphoma that is found only in the tissue or organ where it began (localized). Drugs used in chemotherapy 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), giving the drugs in different doses, and giving the drugs in different combinations may kill more cancer cells.
Detailed Description
PRIMARY OBJECTIVES: l. To determine if a maintenance regimen containing weekly oral methotrexate at 40 mg/m\^2/week will result in an improved disease free survival (DFS) compared to that containing weekly oral methotrexate at 20 mg/m\^2/week in the average-risk (AR) subset of patients with standard-risk B-precursor acute lymphoblastic leukemia (ALL). (Complete effective January 13, 2017) II. To determine whether a reduced-pulses maintenance regimen with vincristine (vincristine sulfate)/dexamethasone pulses delivered every 12 weeks can be used without adversely impacting DFS as compared to pulses given every 4 weeks in the AR subset of patients with standard risk B-precursor ALL. III. To confirm that patients in the low-risk (LR) subset of standard risk B-precursor ALL, based on clinical and cytogenetic features and minimal residual disease (MRD) criteria, can attain a 5 year DFS of at least 95% with either a P9904 based regimen that includes 6 courses of intermediate dose (1 g/m\^2 over 24 hours) methotrexate without alkylating agents or anthracyclines (Arm LR-M), or an outpatient based regimen identical to that of AR patients with reduced vincristine/dexamethasone pulses at 12 week intervals during maintenance (Arm LR-C). IV. To provide standardized treatment and enhanced supportive care to children with standard-risk (SR) Down syndrome B-ALL in order to improve outcomes and facilitate further study of this biologically and clinically unique patient subgroup. V. To improve understanding of the biology of localized B-lineage lymphoblastic lymphoma (B-LLy) and Down syndrome (DS) B-LLy by obtaining biologic data, including fluorescence in situ hybridization (FISH) for recurrent cytogenetic lesions on paraffin specimen, and banking tissue for future research. VI. To describe the 5-year event free survival (EFS) and overall survival (OS) of patients with Murphy stage I and II B-LLy receiving modified AR B-ALL therapy. SECONDARY OBJECTIVES: I. To assess the burden of AR B-ALL therapy as measured by surveys of the child's quality of life, missed days of school/daycare/work by children and parents, family functioning, parental perception of the child's health vulnerability, physical functioning, and emotional distress, 1) overall at different time points during and at the end of therapy, and by 2) comparing children randomized to every 4 week vs. every 12 week dexamethasone/vincristine pulses during maintenance. (Closed to accrual as of April 19, 2013) II. To characterize the onset, severity, and natural history of vincristine associated neuropathy by physical therapists (or occupational therapists) in children undergoing therapy for AR B-ALL, 1) overall at different time points during and at the end of therapy, and by 2) comparing children randomized to every 4 week vs. every 12 week dexamethasone/vincristine pulses during maintenance. (Closed to accrual as of March 15, 2013) TERTIARY OBJECTIVES: I. To explore the correlation of minimal marrow disease (MMD) at diagnosis and outcome for patients with B-LLy. (Closed effective Amendment #5) OUTLINE: All patients receive induction therapy comprising intrathecal (IT) cytarabine on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; dexamethasone orally (PO) or IV twice daily (BID) on days 1-28; pegaspargase IV over 1-2 hours on day 4; and IT methotrexate\* on days 8 and 29. Patients with Philadelphia chromosome-positive disease are eligible to transfer to COG-AALL0622 by day 15 of induction therapy and patients with high-risk (HR) or very high-risk (VHR) disease are eligible to transfer to a COG HR or VHR trial at the end of induction therapy. Patients with standard-risk disease with Down syndrome (DS) who have bone marrow minimal residual disease 0.01% are eligible to transfer to the DS stratum of the HR trial. Patients with induction failure (defined as M3 \[\> 25% lymphoblasts\] on day 29) may be eligible for the COG VHR-acute lymphoblastic leukemia study. NOTE: \*Patients with DS also receive oral leucovorin calcium every 12 hours on days 10-11 and 31-32. STANDARD-RISK WITH DOWN SYNDROME: Consolidation therapy (4 weeks): Patients receive vincristine sulfate IV on day 1; mercaptopurine PO on days 1-28; IT methotrexate on days 1, 8, and 15; and leucovorin calcium PO every 12 hours on days 3-4, 10-11, and 17-18. Interim maintenance I therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41; IT methotrexate on day 31; and leucovorin calcium PO every 12 hours on days 36-34. Delayed-intensification therapy (8 weeks): Patients receive dexamethasone PO or IV BID on days 1-7 and 15-21; vincristine sulfate IV and doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on day 4; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO on days 29-42; cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 29-32 and 33-39; IT methotrexate on days 1 and 29; and leucovorin calcium PO every 12 hours on days 3-4 and 31-32. Interim maintenance II therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41; IT methotrexate on days 1 and 31; and leucovorin calcium PO every 12 hours on days 3-4 and 33-34. Maintenance therapy: Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1. Courses repeat every 12 weeks for 2 years (timed from the start of interim maintenance I therapy). B-LLy: Consolidation therapy (4 weeks): Patients receive vincristine sulfate IV on day 1; mercaptopurine PO on days 1-28; IT methotrexate on days 1, 8, and 15; and leucovorin calcium PO every 12 hours on days 3-4, 10-11, and 17-18. Interim maintenance I therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41; IT methotrexate on day 31; and leucovorin calcium PO every 12 hours on days 36-34. Delayed-intensification therapy (8 weeks): Patients receive dexamethasone PO or IV BID on days 1-7 and 15-21; vincristine sulfate IV and doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on day 4; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO on days 29-42; cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 29-32 and 33-39; IT methotrexate on days 1 and 29; and leucovorin calcium PO every 12 hours on days 3-4 and 31-32. Interim maintenance II therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41; IT methotrexate on days 1 and 31; and leucovorin calcium PO every 12 hours on days 3-4 and 33-34. Maintenance therapy: Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1. Courses repeat every 4 weeks for 2 years (timed from the start of interim maintenance I therapy). AVERAGE-RISK: Consolidation therapy (4 weeks): Patients receive vincristine sulfate IV on day 1; mercaptopurine PO on days 1-28; and IT methotrexate on days 1, 8, and 15.Interim maintenance I therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41 and IT methotrexate on day 31. Delayed intensification therapy (8 weeks): Patients receive dexamethasone PO or IV BID on days 1-7 and 15-21; vincristine sulfate IV and doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on day 4; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO on days 29-42; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; and IT methotrexate on days 1 and 29. Interim maintenance II therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41 and IT methotrexate on days 1 and 31. Maintenance therapy: Patients are randomized to 1 of 4 maintenance therapy treatment arms. Arm A: Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1. Arm B: Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1. Arm C: Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1. Arm D: Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1. In all arms, maintenance therapy courses repeat every 12 weeks for 2 years for girls and for 3 years for boys (timed from the start of interim maintenance I therapy). LOW-RISK: Patients are randomized to 1 of 2 treatment arms. Arm I (LR-M): Consolidation therapy (19 weeks): Beginning one week after completion of induction therapy, patients receive vincristine sulfate IV on days 15, 22, 78, and 85; methotrexate IV over 24 hours and IT methotrexate on days 8, 29, 50, 71, 92, and 113; leucovorin calcium PO or IV on days 9-10, 30-31, 51-52, 72-73, 93-94, and 114-115; dexamethasone PO BID or IV on days 15-21 and 78-84; and PO mercaptopurine on days 1-133.Maintenance therapy: Patients receive vincristine sulfate IV on days 1 and 8; dexamethasone PO BID on days 1-7; methotrexate\* PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, and 106; and mercaptopurine PO on days 1-112. Courses repeat every 16 weeks. Patients also receive IT methotrexate on days 1 and 85 (courses 1 and 4), day 57 (courses 2 and 5), or day 29 (courses 3 and 6). Patients then receive course 7 comprising vincristine sulfate IV on days 1 and 8; dexamethasone PO BID on days 1-7; methotrexate PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64; and mercaptopurine PO on days 1-70. Treatment continues for 2 and ½ years (timed from the date of diagnosis).NOTE: \*Patients do not receive methotrexate PO on the days that they receive IT methotrexate. Arm II (LR-C): Consolidation therapy (4 weeks): Patients receive vincristine sulfate IV on day 1; oral mercaptopurine on days 1-28; and IT methotrexate on days 1, 8, and 15. Interim maintenance I therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41 and IT methotrexate on day 31. Delayed-intensification therapy (8 weeks): Patients receive dexamethasone PO or IV BID on days 1-7 and 15-21; vincristine sulfate IV and doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on day 4; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO on days 29-42; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; and IT methotrexate on days 1 and 29.Interim maintenance II therapy (8 weeks): Patients receive vincristine sulfate IV and methotrexate IV over 2-15 minutes on days 1, 11, 21, 31, and 41 and IT methotrexate on days 1 and 31. Maintenance therapy: Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1. Courses repeat every 12 weeks for 2 years for girls and for 3 years for boys (timed from the start of interim maintenance I therapy). After completion of study treatment, patients are followed up periodically for 10 years from study entry.
Investigators
Eligibility Criteria
Inclusion Criteria
- •B-ALL patients must be enrolled on AALL08B1 or APEC14B1 (if open for the classification of newly diagnosed ALL patients) prior to treatment and enrollment on AALL0932
- •Note: B-LLy patients are not eligible for AALL08B1, and can enroll directly onto AALL0932
- •B-ALL patients must have an initial white blood cell count \< 50,000/uL
- •Patients must have newly diagnosed National Cancer Institute (NCI) Standard Risk B-ALL or B-LLy Murphy stages I or II; patients with Down syndrome are also eligible
- •Note: for B-LLy patients with tissue available for flow cytometry, the criterion for diagnosis should be analogous to B-ALL; for tissue processed by other means (i.e. paraffin blocks), the methodology and criteria for immunophenotypic analysis to establish the diagnosis of B-LLy defined by the submitting institution will be accepted
- •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
Exclusion Criteria
- •With the exception of steroid pretreatment (defined below) or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL0932
- •Patients receiving prior steroid therapy may be eligible for AALL0932
- •Patients with central nervous system 3 (CNS3) leukemia
- •CNS status must be known prior to enrollment; (Note: the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment); B-LLy patients with CNS3 disease are not eligible for this protocol or the COG HR ALL protocol; it is recommended that intrathecal cytarabine be administered at the time of the diagnostic lumbar puncture; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; this is allowed prior to registration; systemic chemotherapy must begin within 72 hours of the first dose of intrathecal therapy
- •B-ALL patients with testicular leukemia are not eligible for AALL0932
- •For B-LLy patients the following additional exclusion criteria apply:
- •T-lymphoblastic lymphoma
- •Morphologically unclassifiable lymphoma
- •Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma
- •CNS3-positive disease or testicular involvement
Arms & Interventions
Arm A (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Dexamethasone
Arm A (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Laboratory Biomarker Analysis
Arm A (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Mercaptopurine
Arm A (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Methotrexate
Arm A (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Quality-of-Life Assessment
Arm A (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Questionnaire Administration
Arm A (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Vincristine Sulfate
Arm B (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Dexamethasone
Arm B (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Laboratory Biomarker Analysis
Arm B (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Mercaptopurine
Arm B (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Methotrexate
Arm SR DS (12-week cycle maintenance)
See Detailed Description
Intervention: Laboratory Biomarker Analysis
Arm B (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Quality-of-Life Assessment
Arm B (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Questionnaire Administration
Arm B (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on days 1, 29, and 57; dexamethasone PO BID on days 1-5, 29-33, and 57-61; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Vincristine Sulfate
Arm B-LLy (4-week cycle maintenance)
See Detailed Description.
Intervention: Cyclophosphamide
Arm B-LLy (4-week cycle maintenance)
See Detailed Description.
Intervention: Cytarabine
Arm B-LLy (4-week cycle maintenance)
See Detailed Description.
Intervention: Dexamethasone
Arm B-LLy (4-week cycle maintenance)
See Detailed Description.
Intervention: Doxorubicin Hydrochloride
Arm B-LLy (4-week cycle maintenance)
See Detailed Description.
Intervention: Laboratory Biomarker Analysis
Arm B-LLy (4-week cycle maintenance)
See Detailed Description.
Intervention: Leucovorin Calcium
Arm B-LLy (4-week cycle maintenance)
See Detailed Description.
Intervention: Mercaptopurine
Arm B-LLy (4-week cycle maintenance)
See Detailed Description.
Intervention: Methotrexate
Arm B-LLy (4-week cycle maintenance)
See Detailed Description.
Intervention: Pegaspargase
Arm B-LLy (4-week cycle maintenance)
See Detailed Description.
Intervention: Quality-of-Life Assessment
Arm B-LLy (4-week cycle maintenance)
See Detailed Description.
Intervention: Questionnaire Administration
Arm B-LLy (4-week cycle maintenance)
See Detailed Description.
Intervention: Thioguanine
Arm B-LLy (4-week cycle maintenance)
See Detailed Description.
Intervention: Vincristine Sulfate
Arm C (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Dexamethasone
Arm C (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Laboratory Biomarker Analysis
Arm C (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Mercaptopurine
Arm C (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Methotrexate
Arm C (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Quality-of-Life Assessment
Arm C (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Questionnaire Administration
Arm C (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Vincristine Sulfate
Arm D (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Dexamethasone
Arm D (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Laboratory Biomarker Analysis
Arm D (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Mercaptopurine
Arm D (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Methotrexate
Arm D (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Quality-of-Life Assessment
Arm D (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Questionnaire Administration
Arm D (risk-adapted chemotherapy)
Patients receive vincristine sulfate IV on day 1; dexamethasone PO BID on days 1-5; higher-dose methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO on days 1-84; and IT methotrexate on day 1.
Intervention: Vincristine Sulfate
Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
Intervention: Cyclophosphamide
Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
Intervention: Cytarabine
Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
Intervention: Dexamethasone
Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
Intervention: Doxorubicin Hydrochloride
Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
Intervention: Laboratory Biomarker Analysis
Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
Intervention: Mercaptopurine
Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
Intervention: Methotrexate
Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
Intervention: Pegaspargase
Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
Intervention: Quality-of-Life Assessment
Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
Intervention: Questionnaire Administration
Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
Intervention: Thioguanine
Arm LR-C (risk-adapted chemotherapy)
Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
Intervention: Vincristine Sulfate
Arm LR-M (risk-adapted chemotherapy)
Patients receive consolidation and maintenance therapy. See detailed description.
Intervention: Dexamethasone
Arm LR-M (risk-adapted chemotherapy)
Patients receive consolidation and maintenance therapy. See detailed description.
Intervention: Laboratory Biomarker Analysis
Arm LR-M (risk-adapted chemotherapy)
Patients receive consolidation and maintenance therapy. See detailed description.
Intervention: Leucovorin Calcium
Arm LR-M (risk-adapted chemotherapy)
Patients receive consolidation and maintenance therapy. See detailed description.
Intervention: Mercaptopurine
Arm LR-M (risk-adapted chemotherapy)
Patients receive consolidation and maintenance therapy. See detailed description.
Intervention: Methotrexate
Arm LR-M (risk-adapted chemotherapy)
Patients receive consolidation and maintenance therapy. See detailed description.
Intervention: Quality-of-Life Assessment
Arm LR-M (risk-adapted chemotherapy)
Patients receive consolidation and maintenance therapy. See detailed description.
Intervention: Questionnaire Administration
Arm LR-M (risk-adapted chemotherapy)
Patients receive consolidation and maintenance therapy. See detailed description.
Intervention: Vincristine Sulfate
Arm SR DS (12-week cycle maintenance)
See Detailed Description
Intervention: Cyclophosphamide
Arm SR DS (12-week cycle maintenance)
See Detailed Description
Intervention: Cytarabine
Arm SR DS (12-week cycle maintenance)
See Detailed Description
Intervention: Dexamethasone
Arm SR DS (12-week cycle maintenance)
See Detailed Description
Intervention: Doxorubicin Hydrochloride
Arm SR DS (12-week cycle maintenance)
See Detailed Description
Intervention: Leucovorin Calcium
Arm SR DS (12-week cycle maintenance)
See Detailed Description
Intervention: Mercaptopurine
Arm SR DS (12-week cycle maintenance)
See Detailed Description
Intervention: Methotrexate
Arm SR DS (12-week cycle maintenance)
See Detailed Description
Intervention: Pegaspargase
Arm SR DS (12-week cycle maintenance)
See Detailed Description
Intervention: Quality-of-Life Assessment
Arm SR DS (12-week cycle maintenance)
See Detailed Description
Intervention: Questionnaire Administration
Arm SR DS (12-week cycle maintenance)
See Detailed Description
Intervention: Thioguanine
Arm SR DS (12-week cycle maintenance)
See Detailed Description
Intervention: Vincristine Sulfate
Outcomes
Primary Outcomes
DFS for SR Down Syndrome Patients With Standardized Treatment and Enhanced Supportive Care
Time Frame: 5.1 years
DFS is calculated as the time from end of Induction to first event (relapse, second malignancy, remission death) or date of last contact. The 5-year DFS and 95% confidence interval for these patients will be estimated.
Overall Survival (OS) for B-LLy Patients
Time Frame: 5 years
OS is calculated as the time from study enrollment to death or date of last contact. The 5-year OS and 95% confidence interval for these patients will be estimated.
Sample Collection of Central Path Review Slides in B-LLy Patients
Time Frame: Up to 1 month
Percent of B-LLy patients who had adequate/usable samples of samples collected will be reported.
DFS in Low Risk (LR) Patients Based on Randomization to 1 of 2 Low-intensity Regimens
Time Frame: 5.1 years
DFS is calculated as the time from randomization at the end of Induction to first event (relapse, second malignancy, remission death) or date of last contact. Five year DFS estimates will be calculated from the point of randomization for both groups. Two-sided 95% confidence intervals will be calculated.
Event Free Survival (EFS) for B-LLy Patients
Time Frame: 5 years
EFS is calculated as the Time from study enrollment to first event (induction failure, relapse, second malignancy, remission death) or date of last contact. The 5-year EFS and 95% confidence interval for these patients will be estimated.
Disease Free Survival (DFS) in Average Risk (AR) Patients Based on the Methotrexate Dose Randomization
Time Frame: 5.7 years
DFS is calculated as the time from randomization at the end of interim maintenance II to first event (relapse, second malignancy, remission death) or date of last contact. Five year DFS estimates will be calculated from the point of randomization for both groups. Two-sided 95% confidence intervals will be calculated.
DFS in Average Risk (AR) Patients Based on the Pulse Frequency Randomization
Time Frame: 5.7 years
DFS is calculated as the time from randomization at the end of interim maintenance II to first event (relapse, second malignancy, remission death) or date of last contact. Five year DFS estimates will be calculated from the point of randomization for both groups. Two-sided 95% confidence intervals will be calculated.
Secondary Outcomes
- Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: Emotional(1.7 years)
- Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: Physical(1 Year)
- Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: Emotional(2 Months)
- Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Emotional(2.5 years)
- Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: Physical(2 Months)
- Burden of Therapy in Boy AR Patients Overall at End of Therapy: School(3.2 Years)
- Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 1: Right(1 Year)
- Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: Emotional(1 year)
- Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: Physical(1.7 years)
- Burden of Therapy in Boy AR Patients Overall at End of Therapy: Physical(3.2 years)
- Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: School(1 Year)
- Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: School(1.7 Years)
- Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): School(2.4 years)
- Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: Social Functioning(1.7 Years)
- Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Social Functioning(2.4 Years)
- Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: Emotional(1.7 years)
- Burden of Therapy in Boy AR Patients Overall at End of Therapy: Emotional(3.2 years)
- Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Physical(2.4 Years)
- Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Emotional(2.4 Years)
- Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: Physical(1.7 Years)
- Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: School(1.7 Years)
- Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): School(2.4 Years)
- Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Social Functioning(2.4 Years)
- Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: School(2 Months)
- Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: Social Functioning(2 Months)
- Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: Social Functioning(1 Year)
- Burden of Therapy in Boy AR Patients Overall at End of Therapy: Social Functioning(3.2 Years)
- Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: Emotional(3.2 Years)
- Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Physical(2.4 Years)
- Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: Social Functioning(3.2 Years)
- Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL 12 Months Post Therapy: Right(4.2 Years)
- Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Left(2.4 Years)
- Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: Physical(3.2 Years)
- Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Consolidation Therapy-Left(2 Months)
- Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Left(2.4 Years)
- Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: School(3.2 Years)
- Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: Social Functioning(1.7 Years)
- Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Consolidation Therapy-Right(2 Months)
- Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 1: Left(1 Year)
- Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL 12 Months Post Therapy: Left(4.2 Years)
- Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Right(2.4 Years)
- Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Right(2.4 Years)