Trial record 1 of 1 for:    AALL0932
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Risk-Adapted Chemotherapy in Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2015 by Children's Oncology Group
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT01190930
First received: August 27, 2010
Last updated: March 3, 2015
Last verified: March 2015

August 27, 2010
March 3, 2015
August 2010
April 2015   (final data collection date for primary outcome measure)
  • Improvement in DFS in AR patients based on the methotrexate randomization [ Time Frame: Time from randomization to 5 years ] [ Designated as safety issue: No ]
  • Determination of whether the DFS in AR patients is adversely affected by the reduced pulses in maintenance [ Time Frame: Time from randomization to 5 years ] [ Designated as safety issue: No ]
  • Determination of whether less intensive therapy will maintain 5 year DFS >= 95% for LR patients on each randomized arm [ Time Frame: Time from end of Induction to 5 years ] [ Designated as safety issue: No ]
  • DFS for Down syndrome patients [ Time Frame: Time from end of Induction to 5 years ] [ Designated as safety issue: No ]
  • Improvement in 5-year disease-free survival (DFS) from 93% to 96% in average-risk (AR) patients based on the methotrexate randomization [ Designated as safety issue: No ]
  • Determination of whether the 5-year DFS in AR patients is adversely affected by the reduced pulses in maintenance [ Designated as safety issue: No ]
  • Determination of whether less intensive therapy will maintain a 5-year DFS ≥ 95% for low-risk patients randomized to 1 of 2 low-intensity regimens [ Designated as safety issue: No ]
  • 5-year DFS for Down syndrome patients [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01190930 on ClinicalTrials.gov Archive Site
  • Burden of therapy in AR patients overall at different time points during and at the end of therapy [ Time Frame: Up to 30 months after beginning of maintenance (off-therapy time point for boys) ] [ Designated as safety issue: No ]
  • Burden of therapy in AR patients randomized to every 4-week vs every 12-week pulses during maintenance therapy [ Time Frame: Up to 30 months after beginning of Maintenance (off-therapy time point for boys) ] [ Designated as safety issue: No ]
  • Burden of therapy in AR patients overall at different time points during and at the end of therapy [ Designated as safety issue: No ]
  • Burden of therapy in AR patients randomized to every 4-week vs every 12-week pulses during maintenance therapy [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Risk-Adapted Chemotherapy in Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia
Treatment of Patients With Newly Diagnosed Standard Risk B-Precursor Acute Lymphoblastic Leukemia (ALL)

This partially randomized phase III clinical trial is studying different combinations of risk-adapted chemotherapy regimens and their side effects and comparing how well they work in treating younger patients with newly diagnosed standard-risk acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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.

PRIMARY OBJECTIVES:

l. To determine if a maintenance regimen containing once 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 pediatric patients with standard-risk (SR) B-precursor acute lymphoblastic leukemia (ALL).

II. To determine whether a reduced-pulses maintenance regimen with 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 SR B-precursor ALL.

III. To confirm that patients in the low-risk (LR) subset of SR 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 sulfate/dexamethasone pulses at 12-week intervals during maintenance (Arm LR-C).

IV. To provide standardized treatment and enhanced supportive care to children with SR Down syndrome-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-LLy and DS B-LLy by obtaining biologic data, including FISH for recurrent cytogenetic lesions on paraffin specimen, and banking tissue for future research.

VI. To describe the 5-year 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-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 overall at different time points during and at the end of therapy.

II. To assess the burden of AR-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 by comparing children randomized to every 4-week vs every 12-week dexamethasone/vincristine sulfate pulses during maintenance therapy.

III. To characterize the onset, severity, and natural history of vincristine associated neuropathy by physical therapists (or occupational therapists) in children undergoing therapy for AR-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.

IV. 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.

V. To explore the correlation of minimal marrow disease (MMD) at diagnosis and outcome for patients with B-LLy.

OUTLINE: This is a multicenter study.

All patients receive induction therapy comprising intrathecal (IT) cytarabine on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; dexamethasone orally 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; oral mercaptopurine on days 1-28; IT methotrexate on days 1, 8, and 15; and oral leucovorin calcium 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 oral leucovorin calcium every 12 hours on days 36-34. Delayed-intensification therapy (8 weeks): Patients receive dexamethasone orally 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; oral thioguanine on days 29-42; cytarabine IV over 1-15 minutes or subcutaneously (SC) on days 29-32 and 33-39; IT methotrexate on days 1 and 29; and oral leucovorin calcium 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 oral leucovorin calcium every 12 hours on days 3-4 and 33-34. Maintenance therapy: Patients receive vincristine sulfate IV on day 1; oral dexamethasone BID on days 1-5; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine 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).

AVERAGE-RISK:

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 orally 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; oral thioguanine on days 29-42; cytarabine IV over 15-30 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; oral dexamethasone BID on days 1-5, 29-33, and 57-61; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and IT methotrexate on day 1.

Arm B: Patients receive vincristine sulfate IV on days 1, 29, and 57; oral dexamethasone BID on days 1-5, 29-33, and 57-61; higher-dose oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and IT methotrexate on day 1.

Arm C: Patients receive vincristine sulfate IV on day 1; oral dexamethasone BID on days 1-5; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and IT methotrexate on day 1.

Arm D: Patients receive vincristine sulfate IV on day 1; oral dexamethasone BID on days 1-5; higher-dose oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine 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 orally or IV on days 9-10, 30-31, 51-52, 72-73, 93-94, and 114-115; dexamethasone orally or IV BID on days 15-21 and 78-84; and oral mercaptopurine on days 1-133.Maintenance therapy: Patients receive vincristine sulfate IV on days 1 and 8; oral dexamethasone BID on days 1-7; oral methotrexate* on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, and 106; and oral mercaptopurine 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; oral dexamethasone BID on days 1-7; oral methotrexate on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64; and oral mercaptopurine on days 1-70. Treatment continues for 2 and ½ years (timed from the date of diagnosis).NOTE: *Patients do not receive oral methotrexate 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 orally 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; oral thioguanine on days 29-42; cytarabine IV over 1-15 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; oral dexamethasone BID on days 1-5; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine 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).

Blood samples may be collected periodically for research studies and patients may complete quality-of-life surveys periodically.

After completion of study treatment, patients are followed up periodically for 10 years.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • B-cell Childhood Acute Lymphoblastic Leukemia
  • Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia
  • Untreated Adult Acute Lymphoblastic Leukemia
  • Untreated Childhood Acute Lymphoblastic Leukemia
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
    • Adriamycin PFS
    • Adriamycin RDF
  • Drug: cytarabine
    Given IT, IV, or SC
    Other Names:
    • ARA-C
    • arabinofuranosylcytosine
    • arabinosylcytosine
    • Cytosar-U
    • cytosine arabinoside
  • Drug: vincristine sulfate
    Given IV
    Other Names:
    • leurocristine sulfate
    • VCR
    • Vincasar PFS
  • Drug: dexamethasone
    Given orally (PO) or IV
    Other Names:
    • Aeroseb-Dex
    • Decaderm
    • Decadron
    • DM
    • DXM
  • Drug: pegaspargase
    Given IV
    Other Names:
    • L-asparaginase with polyethylene glycol
    • Oncaspar
    • PEG-ASP
    • PEG-L-asparaginase
  • Drug: methotrexate
    Given IT, PO, or IV
    Other Names:
    • amethopterin
    • Folex
    • methylaminopterin
    • Mexate
    • MTX
  • Drug: mercaptopurine tablet
    Given PO
    Other Names:
    • 6-mercaptopurine
    • 6-MP
    • Leukerin
    • MP
  • Drug: leucovorin calcium
    Given PO
    Other Names:
    • CF
    • CFR
    • LV
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: thioguanine
    Given PO
    Other Name: 6-TG
  • Procedure: quality-of-life assessment
    Ancillary studies
    Other Name: quality of life assessment
  • Other: questionnaire administration
    Ancillary studies
  • Other: laboratory biomarker analysis
    Correlative studies
  • Experimental: Arm A - B-ALL Average Risk Maintenance Therapy
    Patients receive vincristine sulfate IV on days 1, 29, and 57; oral dexamethasone BID on days 1-5, 29-33, and 57-61; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and IT methotrexate on day 1.
    Interventions:
    • Drug: vincristine sulfate
    • Drug: dexamethasone
    • Drug: methotrexate
    • Drug: mercaptopurine tablet
    • Procedure: quality-of-life assessment
    • Other: questionnaire administration
    • Other: laboratory biomarker analysis
  • Experimental: Arm B - B-ALL Average Risk Maintenance Therapy
    Patients receive vincristine sulfate IV on days 1, 29, and 57; oral dexamethasone BID on days 1-5, 29-33, and 57-61; higher-dose oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and IT methotrexate on day 1.
    Interventions:
    • Drug: vincristine sulfate
    • Drug: dexamethasone
    • Drug: methotrexate
    • Drug: mercaptopurine tablet
    • Procedure: quality-of-life assessment
    • Other: questionnaire administration
    • Other: laboratory biomarker analysis
  • Experimental: Arm C - B-ALL Average Risk Maintenance Therapy
    Patients receive vincristine sulfate IV on day 1; oral dexamethasone BID on days 1-5; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and IT methotrexate on day 1.
    Interventions:
    • Drug: vincristine sulfate
    • Drug: dexamethasone
    • Drug: methotrexate
    • Drug: mercaptopurine tablet
    • Procedure: quality-of-life assessment
    • Other: questionnaire administration
    • Other: laboratory biomarker analysis
  • Experimental: Arm D - B-ALL Average Risk Maintenance Therapy
    Patients receive vincristine sulfate IV on day 1; oral dexamethasone BID on days 1-5; higher-dose oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and IT methotrexate on day 1.
    Interventions:
    • Drug: vincristine sulfate
    • Drug: dexamethasone
    • Drug: methotrexate
    • Drug: mercaptopurine tablet
    • Procedure: quality-of-life assessment
    • Other: questionnaire administration
    • Other: laboratory biomarker analysis
  • Experimental: Arm LR-M - B-ALL Low Risk Post Induction Therapy
    Consolidation (19 wks): Vincristine sulfate IV days 15, 22, 78, & 85; methotrexate IV & IT methotrexate days 8, 29, 50, 71, 92, & 113; leucovorin calcium orally or IV days 9-10, 30-31, 51-52, 72-73, 93-94, & 114-115; dexamethasone orally or IV days 15-21 & 78-84; & oral mercaptopurine on days 1-133. Maintenance: Vincristine sulfate IV days 1 & 8; oral dexamethasone days 1-7; oral methotrexate days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, & 106; & oral mercaptopurine days 1-112. Courses repeat every 16 wks. IT methotrexate days 1 & 85 (courses 1 & 4), day 57 (courses 2 & 5), or day 29 (courses 3 & 6). Course 7 Vincristine sulfate IV days 1 & 8; oral dexamethasone days 1-7; oral methotrexate days 1, 8, 15, 22, 29, 36, 43, 50, 57, & 64; and oral mercaptopurine days 1-70. Treatment continues for 2½ years (timed from the date of diagnosis). NOTE: *Patients do not receive oral methotrexate on the days that they receive IT methotrexate.
    Interventions:
    • Drug: vincristine sulfate
    • Drug: dexamethasone
    • Drug: methotrexate
    • Drug: mercaptopurine tablet
    • Drug: leucovorin calcium
    • Procedure: quality-of-life assessment
    • Other: questionnaire administration
    • Other: laboratory biomarker analysis
  • Experimental: Arm LR-C - B-ALL Low Risk Post Induction Therapy
    Consolidation: Vincristine sulfate IV day 1; oral mercaptopurine days 1-28; & IT methotrexate days 1, 8, & 15. Interim maintenance I (8 weeks): Vincristine sulfate IV & methotrexate IV days 1, 11, 21, 31, & 41 & IT methotrexate day 31. Delayed-intensification (8 weeks): Dexamethasone orally or IV BID days 1-7 & 15-21; vincristine sulfate IV & doxorubicin hydrochloride IV days 1, 8, & 15; pegaspargase IV day 4; cyclophosphamide IV day 29; oral thioguanine days 29-42; cytarabine IV or SC days 29-32 & 36-39; & IT methotrexate on days 1 & 29.Interim maintenance II (8 weeks): Vincristine sulfate IV & methotrexate IV days 1, 11, 21, 31, & 41 & IT methotrexate days 1 & 31. Maintenance: Vincristine sulfate IV day 1; oral dexamethasone days 1-5; oral methotrexate days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, & 78; oral mercaptopurine days 1-84; & IT methotrexate day 1. Courses repeat every 12 wks for 2 yrs for girls & for 3 yrs for boys (timed from the start of interim maintenance I therapy).
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: cytarabine
    • Drug: vincristine sulfate
    • Drug: dexamethasone
    • Drug: pegaspargase
    • Drug: methotrexate
    • Drug: mercaptopurine tablet
    • Drug: cyclophosphamide
    • Drug: thioguanine
    • Procedure: quality-of-life assessment
    • Other: questionnaire administration
    • Other: laboratory biomarker analysis
  • Experimental: Arm LLy - B-LLY Non Down Syndrome Post Induction Therapy
    Maintenance: Patients receive vincristine sulfate IV on days 1, 29, and 57; oral dexamethasone BID on days 1-5, 29-33, and 57-61; oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and IT methotrexate on day 1.
    Interventions:
    • Drug: vincristine sulfate
    • Drug: dexamethasone
    • Drug: methotrexate
    • Drug: mercaptopurine tablet
    • Procedure: quality-of-life assessment
    • Other: questionnaire administration
    • Other: laboratory biomarker analysis
  • Experimental: All patients (B-ALL and B-LLy) Induction Therapy
    IT cytarabine day 1; vincristine sulfate IV days 1, 8, 15, & 22; dexamethasone orally or IV days 1-28; pegaspargase IV day 4; & IT methotrexate days 8 & 29. Philadelphia chromosome-positive patients are eligible to transfer to COG-AALL0622 by day 15 of induction therapy & 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 days 10-11 & 31-32.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: vincristine sulfate
    • Drug: dexamethasone
    • Drug: methotrexate
    • Procedure: quality-of-life assessment
    • Other: questionnaire administration
    • Other: laboratory biomarker analysis
  • Experimental: Arm DS - B-ALL and B-LLy Down Syndrome Post-Induction Therapy
    Patients receive vincristine sulfate IV on day 1; oral dexamethasone BID on days 1-5; higher-dose oral methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; oral mercaptopurine on days 1-84; and IT methotrexate on day 1.
    Interventions:
    • Drug: vincristine sulfate
    • Drug: dexamethasone
    • Drug: methotrexate
    • Drug: mercaptopurine tablet
    • Procedure: quality-of-life assessment
    • Other: questionnaire administration
    • Other: laboratory biomarker analysis
  • Experimental: B-ALL Avg Risk Post-Induction/Pre-Maintenance Therapy
    Consolidation: Vincristine sulfate IV day 1; oral mercaptopurine days 1-28; & IT methotrexate days 1, 8, & 15. Interim maintenance I (8 weeks): Vincristine sulfate IV & methotrexate IV days 1, 11, 21, 31, & 41 & IT methotrexate day 31. Delayed-intensification (8 weeks): Dexamethasone orally or IV BID days 1-7 & 15-21; vincristine sulfate IV & doxorubicin hydrochloride IV days 1, 8, & 15; pegaspargase IV day 4; cyclophosphamide IV day 29; oral thioguanine days 29-42; cytarabine IV or SC days 29-32 & 36-39; & IT methotrexate on days 1 & 29.Interim maintenance II (8 weeks): Vincristine sulfate IV & methotrexate IV days 1, 11, 21, 31, & 41 & IT methotrexate days 1 & 31. Maintenance randomized to Arm A, Arm B, Arm C or Arm D.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: vincristine sulfate
    • Drug: dexamethasone
    • Drug: pegaspargase
    • Drug: methotrexate
    • Drug: cyclophosphamide
    • Drug: thioguanine
    • Procedure: quality-of-life assessment
    • Other: questionnaire administration
  • Experimental: B-ALL and B-LLy Down Syndrome Induction Therapy
    IT cytarabine day 1; vincristine sulfate IV days 1, 8, 15, & 22; dexamethasone orally or IV days 1-28; pegaspargase IV day 4; & IT methotrexate days 8 & 29. Oral leucovorin calcium every 12 hours days 10-11 & 31-32.
    Interventions:
    • Drug: doxorubicin hydrochloride
    • Drug: vincristine sulfate
    • Drug: dexamethasone
    • Drug: methotrexate
    • Drug: leucovorin calcium
    • Procedure: quality-of-life assessment
    • Other: questionnaire administration
    • Other: laboratory biomarker analysis
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
5872
Not Provided
April 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • B-ALL patients must be enrolled on AALL08B1 prior to treatment and enrollment on AALL0932
  • Patients must have newly diagnosed 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
  • Meets the criteria for one of the following risk groups after induction therapy

    • Low-risk (LR) disease, defined as meeting the following criteria:

      • Favorable genetics: the presence of simultaneous trisomies of chromosome 4 and 10 (double trisomy; DT) or ETV6/RUNX1 fusion
      • Day 8 peripheral blood (PB) minimal residual disease (MRD) < 0.01%
      • Day 29 bone marrow (BM) MRD < 0.01%
      • No CNS2*, CNS3*, or testicular† leukemia
      • No steroid pretreatment
      • No Down syndrome (DS)
    • Average-risk disease, defined as meeting one of the following sets of criteria:

      • Favorable genetics: the presence of DT or ETV6/RUNX1 fusions
      • Day 8 PB MRD ≥ 0.01% or CNS2* status
      • Day 29 BM MRD < 0.01%
      • No CNS3* or testicular† leukemia
      • No DS
      • Neither favorable nor unfavorable cytogenetics‡
      • Day 8 PB MRD < 1%
      • Day 29 BM MRD < 0.01%
      • No CNS3* or testicular† leukemia
      • No DS
    • Standard-risk with Down syndrome (DS), defined as meeting the following criteria:

      • No mixed-lineage leukemia (MLL)-rearrangement, hypodiploidy**, or Philadelphia chromosome-positive (Ph+) disease††
      • Day 29 BM MRD < 0.01%‡‡
      • No CNS3* or testicular† leukemia
  • WBC count < 50,000/mm^3
  • No prior cytotoxic chemotherapy for the current diagnosis of ALL or any cancer diagnosed previously

    • Steroids* and intrathecal cytarabine for the current diagnosis of ALL allowed

      • Inhalational steroids are not considered as pretreatment
  • Patients with testicular leukemia are not eligible for AALL0932
Both
1 Year to 30 Years
No
Contact: Peter Adamson, MD 612-624-8651 Adamson@email.chop.edu
United States,   Australia,   Canada,   New Zealand,   Switzerland
 
NCT01190930
AALL0932, NCI-2011-02599, CDR0000683227, AALL0932, AALL0932, U10CA098543
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Principal Investigator: Anne Angiolillo, MD Children's Oncology Group
Children's Oncology Group
March 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP