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Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01190930
Recruitment Status : Active, not recruiting
First Posted : August 30, 2010
Results First Posted : June 23, 2020
Last Update Posted : July 12, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE August 27, 2010
First Posted Date  ICMJE August 30, 2010
Results First Submitted Date  ICMJE March 25, 2020
Results First Posted Date  ICMJE June 23, 2020
Last Update Posted Date July 12, 2022
Actual Study Start Date  ICMJE August 9, 2010
Actual Primary Completion Date March 31, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2020)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: August 27, 2010)
  • Improvement in 5-year disease-free survival (DFS) from 93% to 96% in average-risk (AR) patients based on the methotrexate randomization
  • Determination of whether the 5-year DFS in AR patients is adversely affected by the reduced pulses in maintenance
  • 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
  • 5-year DFS for Down syndrome patients
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 26, 2021)
  • Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: Emotional [ Time Frame: 2 Months ]
    Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: Emotional [ Time Frame: 1 year ]
    Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: Emotional [ Time Frame: 1.7 years ]
    Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Emotional [ Time Frame: 2.5 years ]
    Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in Boy AR Patients Overall at End of Therapy: Emotional [ Time Frame: 3.2 years ]
    Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Genetic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: Physical [ Time Frame: 2 Months ]
    Age and gender standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: Physical [ Time Frame: 1 Year ]
    Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: Physical [ Time Frame: 1.7 years ]
    Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Physical [ Time Frame: 2.4 Years ]
    Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in Boy AR Patients Overall at End of Therapy: Physical [ Time Frame: 3.2 years ]
    Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: School [ Time Frame: 2 Months ]
    Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: School [ Time Frame: 1 Year ]
    Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: School [ Time Frame: 1.7 Years ]
    Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): School [ Time Frame: 2.4 years ]
    Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in Boy AR Patients Overall at End of Therapy: School [ Time Frame: 3.2 Years ]
    Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Consolidation Therapy: Social Functioning [ Time Frame: 2 Months ]
    Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 1: Social Functioning [ Time Frame: 1 Year ]
    Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 4: Social Functioning [ Time Frame: 1.7 Years ]
    Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients Overall at End of Maintenance Cycle 7 (Boys)/End of Therapy (Girls): Social Functioning [ Time Frame: 2.4 Years ]
    Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in Boy AR Patients Overall at End of Therapy: Social Functioning [ Time Frame: 3.2 Years ]
    Age standardized Quality of life, measured by the Social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated with mean and standard deviation reported.
  • Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: Emotional [ Time Frame: 1.7 years ]
    Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with means and standard deviation reported.
  • 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 [ Time Frame: 2.4 Years ]
    Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.
  • Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: Emotional [ Time Frame: 3.2 Years ]
    Age standardized Quality of life, measured by the emotional subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.
  • Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: Physical [ Time Frame: 1.7 Years ]
    Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with means and standard deviation reported.
  • 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 [ Time Frame: 2.4 Years ]
    Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.
  • Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: Physical [ Time Frame: 3.2 Years ]
    Age standardized Quality of life, measured by the physical subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.
  • Burden of Therapy in AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Maintenance Cycle 4: School [ Time Frame: 1.7 Years ]
    Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with means and standard deviation reported.
  • 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 [ Time Frame: 2.4 Years ]
    Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.
  • Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: School [ Time Frame: 3.2 Years ]
    Age standardized Quality of life, measured by the school subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.
  • 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 [ Time Frame: 1.7 Years ]
    Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with means and standard deviation reported.
  • 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 [ Time Frame: 2.4 Years ]
    Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.
  • Burden of Therapy in Boy AR Patients by Vincristine Pulse Frequency Randomization Groups (4 Week vs. 12 Week) at End of Therapy: Social Functioning [ Time Frame: 3.2 Years ]
    Age standardized Quality of life, measured by the social functioning subscale of Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL), will be calculated for each group with mean and standard deviation reported.
  • Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Consolidation Therapy-Right [ Time Frame: 2 Months ]
    Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.
  • Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Consolidation Therapy-Left [ Time Frame: 2 Months ]
    Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.
  • Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 1: Right [ Time Frame: 1 Year ]
    Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.
  • Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL at End of Maintenance Cycle 1: Left [ Time Frame: 1 Year ]
    Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.
  • 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 [ Time Frame: 2.4 Years ]
    Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.
  • 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 [ Time Frame: 2.4 Years ]
    Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.
  • Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL 12 Months Post Therapy: Right [ Time Frame: 4.2 Years ]
    Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.
  • Characterize Vincristine-associated Neuropathy in Children Undergoing Therapy for Average Risk (AR) ALL 12 Months Post Therapy: Left [ Time Frame: 4.2 Years ]
    Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for the cohort will be reported.
  • 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 [ Time Frame: 2.4 Years ]
    Strength in the right ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for each randomization group will be reported.
  • 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 [ Time Frame: 2.4 Years ]
    Strength in the left ankle dorsiflexors averaged over two measurements. Age and gender standardized mean and standard deviation for each randomization group will be reported.
Original Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2010)
  • Burden of therapy in AR patients overall at different time points during and at the end of therapy
  • Burden of therapy in AR patients randomized to every 4-week vs every 12-week pulses during maintenance therapy
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma
Official Title  ICMJE Treatment of Patients With Newly Diagnosed Standard Risk B-Lymphoblastic Leukemia (B-ALL) or Localized B-Lineage Lymphoblastic Lymphoma (B-LLy)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Lymphoblastic Leukemia
  • Adult B Lymphoblastic Lymphoma
  • Ann Arbor Stage I B Lymphoblastic Lymphoma
  • Ann Arbor Stage II B Lymphoblastic Lymphoma
  • Childhood B Acute Lymphoblastic Leukemia
  • Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1
  • Childhood B Lymphoblastic Lymphoma
  • Down Syndrome
  • Hypodiploid B Acute Lymphoblastic Leukemia
  • Philadelphia Chromosome Positive
Intervention  ICMJE
  • Drug: Cyclophosphamide
    Given IV
    Other Names:
    • (-)-Cyclophosphamide
    • 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate
    • Carloxan
    • Ciclofosfamida
    • Ciclofosfamide
    • Cicloxal
    • Clafen
    • Claphene
    • CP monohydrate
    • CTX
    • CYCLO-cell
    • Cycloblastin
    • Cycloblastine
    • Cyclophospham
    • Cyclophosphamid monohydrate
    • Cyclophosphamide Monohydrate
    • Cyclophosphamidum
    • Cyclophosphan
    • Cyclophosphane
    • Cyclophosphanum
    • Cyclostin
    • Cyclostine
    • Cytophosphan
    • Cytophosphane
    • Cytoxan
    • Fosfaseron
    • Genoxal
    • Genuxal
    • Ledoxina
    • Mitoxan
    • Neosar
    • Revimmune
    • Syklofosfamid
    • WR- 138719
  • Drug: Cytarabine
    Given IT, IV, or SC
    Other Names:
    • .beta.-Cytosine arabinoside
    • 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone
    • 1-.beta.-D-Arabinofuranosylcytosine
    • 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone
    • 1-Beta-D-arabinofuranosylcytosine
    • 1.beta.-D-Arabinofuranosylcytosine
    • 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-
    • 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-
    • Alexan
    • Ara-C
    • ARA-cell
    • Arabine
    • Arabinofuranosylcytosine
    • Arabinosylcytosine
    • Aracytidine
    • Aracytin
    • Aracytine
    • Beta-Cytosine Arabinoside
    • CHX-3311
    • Cytarabinum
    • Cytarbel
    • Cytosar
    • Cytosine Arabinoside
    • Cytosine-.beta.-arabinoside
    • Cytosine-beta-arabinoside
    • Erpalfa
    • Starasid
    • Tarabine PFS
    • U 19920
    • U-19920
    • Udicil
    • WR-28453
  • Drug: Dexamethasone
    Given orally (PO) or IV
    Other Names:
    • Aacidexam
    • Adexone
    • Aknichthol Dexa
    • Alba-Dex
    • Alin
    • Alin Depot
    • Alin Oftalmico
    • Amplidermis
    • Anemul mono
    • Auricularum
    • Auxiloson
    • Baycadron
    • Baycuten
    • Baycuten N
    • Cortidexason
    • Cortisumman
    • Decacort
    • Decadrol
    • Decadron
    • Decadron DP
    • Decalix
    • Decameth
    • Decasone R.p.
    • Dectancyl
    • Dekacort
    • Deltafluorene
    • Deronil
    • Desamethasone
    • Desameton
    • Dexa-Mamallet
    • Dexa-Rhinosan
    • Dexa-Scheroson
    • Dexa-sine
    • Dexacortal
    • Dexacortin
    • Dexafarma
    • Dexafluorene
    • Dexalocal
    • Dexamecortin
    • Dexameth
    • Dexamethasone Intensol
    • Dexamethasonum
    • Dexamonozon
    • Dexapos
    • Dexinoral
    • Dexone
    • Dinormon
    • Dxevo
    • Fluorodelta
    • Fortecortin
    • Gammacorten
    • Hexadecadrol
    • Hexadrol
    • Lokalison-F
    • Loverine
    • Methylfluorprednisolone
    • Millicorten
    • Mymethasone
    • Orgadrone
    • Spersadex
    • TaperDex
    • Visumetazone
    • ZoDex
  • Drug: Doxorubicin Hydrochloride
    Given IV
    Other Names:
    • 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI)
    • ADM
    • Adriacin
    • Adriamycin
    • Adriamycin Hydrochloride
    • Adriamycin PFS
    • Adriamycin RDF
    • ADRIAMYCIN, HYDROCHLORIDE
    • Adriamycine
    • Adriblastina
    • Adriblastine
    • Adrimedac
    • Chloridrato de Doxorrubicina
    • DOX
    • DOXO-CELL
    • Doxolem
    • Doxorubicin HCl
    • Doxorubicin.HCl
    • Doxorubin
    • Farmiblastina
    • FI 106
    • FI-106
    • hydroxydaunorubicin
    • Rubex
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Drug: Leucovorin Calcium
    Given PO
    Other Names:
    • Adinepar
    • Calcifolin
    • Calcium (6S)-Folinate
    • Calcium Folinate
    • Calcium Leucovorin
    • Calfolex
    • Calinat
    • Cehafolin
    • Citofolin
    • Citrec
    • Citrovorum Factor
    • Cromatonbic Folinico
    • Dalisol
    • Disintox
    • Divical
    • Ecofol
    • Emovis
    • Factor, Citrovorum
    • Flynoken A
    • Folaren
    • Folaxin
    • FOLI-cell
    • Foliben
    • Folidan
    • Folidar
    • Folinac
    • Folinate Calcium
    • folinic acid
    • Folinic Acid Calcium Salt Pentahydrate
    • Folinoral
    • Folinvit
    • Foliplus
    • Folix
    • Imo
    • Lederfolat
    • Lederfolin
    • Leucosar
    • leucovorin
    • Rescufolin
    • Rescuvolin
    • Tonofolin
    • Wellcovorin
  • Drug: Mercaptopurine
    Given PO
    Other Names:
    • 3H-Purine-6-thiol
    • 6 MP
    • 6 Thiohypoxanthine
    • 6 Thiopurine
    • 6-Mercaptopurine
    • 6-Mercaptopurine Monohydrate
    • 6-MP
    • 6-Purinethiol
    • 6-Thiopurine
    • 6-Thioxopurine
    • 6H-Purine-6-thione, 1,7-dihydro- (9CI)
    • 7-Mercapto-1,3,4,6-tetrazaindene
    • Alti-Mercaptopurine
    • Azathiopurine
    • Bw 57-323H
    • Flocofil
    • Ismipur
    • Leukerin
    • Leupurin
    • Mercaleukim
    • Mercaleukin
    • Mercaptina
    • Mercaptopurinum
    • Mercapurin
    • Mern
    • NCI-C04886
    • Puri-Nethol
    • Purimethol
    • Purine, 6-mercapto-
    • Purine-6-thiol (8CI)
    • Purine-6-thiol, monohydrate
    • Purinethiol
    • Purinethol
    • U-4748
    • WR-2785
  • Drug: Methotrexate
    Given IT, PO, or IV
    Other Names:
    • Abitrexate
    • Alpha-Methopterin
    • Amethopterin
    • Brimexate
    • CL 14377
    • CL-14377
    • Emtexate
    • Emthexat
    • Emthexate
    • Farmitrexat
    • Fauldexato
    • Folex
    • Folex PFS
    • Lantarel
    • Ledertrexate
    • Lumexon
    • Maxtrex
    • Medsatrexate
    • Metex
    • Methoblastin
    • Methotrexate LPF
    • Methotrexate Methylaminopterin
    • Methotrexatum
    • Metotrexato
    • Metrotex
    • Mexate
    • Mexate-AQ
    • MTX
    • Novatrex
    • Rheumatrex
    • Texate
    • Tremetex
    • Trexeron
    • Trixilem
    • WR-19039
  • Drug: Pegaspargase
    Given IV
    Other Names:
    • L-Asparaginase with Polyethylene Glycol
    • Oncaspar
    • Oncaspar-IV
    • PEG-Asparaginase
    • PEG-L-Asparaginase
    • PEG-L-Asparaginase (Enzon - Kyowa Hakko)
    • PEGLA
    • Polyethylene Glycol L-Asparaginase
    • Polyethylene Glycol-L-Asparaginase
  • Other: Quality-of-Life Assessment
    Ancillary studies
    Other Name: Quality of Life Assessment
  • Other: Questionnaire Administration
    Ancillary studies
  • Drug: Thioguanine
    Given PO
    Other Names:
    • 2-Amino 6MP
    • 2-Amino-1,7-dihydro-6H-purine-6-thione
    • 2-Amino-6-mercaptopurine
    • 2-Amino-6-purinethiol
    • 2-Aminopurin-6-thiol
    • 2-Aminopurine-6(1H)-thione
    • 2-Aminopurine-6-thiol
    • 2-Aminopurine-6-thiol Hemihydrate
    • 2-Mercapto-6-aminopurine
    • 6-Amino-2-mercaptopurine
    • 6-Mercapto-2-aminopurine
    • 6-Mercaptoguanine
    • 6-TG
    • 6H-Purine-6-thione, 2-amino-1,7-dihydro- (9CI)
    • BW 5071
    • Lanvis
    • Tabloid
    • Thioguanine Hemihydrate
    • Thioguanine Hydrate
    • Tioguanin
    • Tioguanine
    • Wellcome U3B
    • WR-1141
    • X 27
  • Drug: Vincristine Sulfate
    Given IV
    Other Names:
    • Kyocristine
    • Leurocristine Sulfate
    • Leurocristine, sulfate
    • Oncovin
    • Vincasar
    • Vincosid
    • Vincrex
    • Vincristine, sulfate
Study Arms  ICMJE
  • Experimental: 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.
    Interventions:
    • Drug: Dexamethasone
    • Other: Laboratory Biomarker Analysis
    • Drug: Mercaptopurine
    • Drug: Methotrexate
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Drug: Vincristine Sulfate
  • Experimental: 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.
    Interventions:
    • Drug: Dexamethasone
    • Other: Laboratory Biomarker Analysis
    • Drug: Mercaptopurine
    • Drug: Methotrexate
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Drug: Vincristine Sulfate
  • Experimental: Arm B-LLy (4-week cycle maintenance)
    See Detailed Description.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Cytarabine
    • Drug: Dexamethasone
    • Drug: Doxorubicin Hydrochloride
    • Other: Laboratory Biomarker Analysis
    • Drug: Leucovorin Calcium
    • Drug: Mercaptopurine
    • Drug: Methotrexate
    • Drug: Pegaspargase
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Drug: Thioguanine
    • Drug: Vincristine Sulfate
  • Experimental: 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.
    Interventions:
    • Drug: Dexamethasone
    • Other: Laboratory Biomarker Analysis
    • Drug: Mercaptopurine
    • Drug: Methotrexate
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Drug: Vincristine Sulfate
  • Experimental: 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.
    Interventions:
    • Drug: Dexamethasone
    • Other: Laboratory Biomarker Analysis
    • Drug: Mercaptopurine
    • Drug: Methotrexate
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Drug: Vincristine Sulfate
  • Experimental: Arm LR-C (risk-adapted chemotherapy)
    Patients receive consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy. See detailed description.
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Cytarabine
    • Drug: Dexamethasone
    • Drug: Doxorubicin Hydrochloride
    • Other: Laboratory Biomarker Analysis
    • Drug: Mercaptopurine
    • Drug: Methotrexate
    • Drug: Pegaspargase
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Drug: Thioguanine
    • Drug: Vincristine Sulfate
  • Experimental: Arm LR-M (risk-adapted chemotherapy)
    Patients receive consolidation and maintenance therapy. See detailed description.
    Interventions:
    • Drug: Dexamethasone
    • Other: Laboratory Biomarker Analysis
    • Drug: Leucovorin Calcium
    • Drug: Mercaptopurine
    • Drug: Methotrexate
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Drug: Vincristine Sulfate
  • Experimental: Arm SR DS (12-week cycle maintenance)
    See Detailed Description
    Interventions:
    • Drug: Cyclophosphamide
    • Drug: Cytarabine
    • Drug: Dexamethasone
    • Drug: Doxorubicin Hydrochloride
    • Other: Laboratory Biomarker Analysis
    • Drug: Leucovorin Calcium
    • Drug: Mercaptopurine
    • Drug: Methotrexate
    • Drug: Pegaspargase
    • Other: Quality-of-Life Assessment
    • Other: Questionnaire Administration
    • Drug: Thioguanine
    • Drug: Vincristine Sulfate
Publications * Angiolillo AL, Schore RJ, Kairalla JA, Devidas M, Rabin KR, Zweidler-McKay P, Borowitz MJ, Wood B, Carroll AJ, Heerema NA, Relling MV, Hitzler J, Lane AR, Maloney KW, Wang C, Bassal M, Carroll WL, Winick NJ, Raetz EA, Loh ML, Hunger SP. Excellent Outcomes With Reduced Frequency of Vincristine and Dexamethasone Pulses in Standard-Risk B-Lymphoblastic Leukemia: Results From Children's Oncology Group AALL0932. J Clin Oncol. 2021 May 1;39(13):1437-1447. doi: 10.1200/JCO.20.00494. Epub 2021 Jan 7.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: June 5, 2020)
9350
Original Estimated Enrollment  ICMJE
 (submitted: August 27, 2010)
5760
Estimated Study Completion Date  ICMJE March 31, 2028
Actual Primary Completion Date March 31, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
    • M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow
    • Female patients who are pregnant are ineligible
    • Lactating females are not eligible unless they have agreed not to breastfeed their infants
    • 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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   Ireland,   New Zealand,   Puerto Rico,   Switzerland,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01190930
Other Study ID Numbers  ICMJE AALL0932
NCI-2011-02599 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
CDR0000683227
11-00080
AALL0932 ( Other Identifier: Children's Oncology Group )
AALL0932 ( Other Identifier: CTEP )
U10CA180886 ( U.S. NIH Grant/Contract )
U10CA098543 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Children's Oncology Group
Original Responsible Party Gregory H. Reaman, Children's Oncology Group - Group Chair Office
Current Study Sponsor  ICMJE Children's Oncology Group
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Anne L Angiolillo Children's Oncology Group
PRS Account Children's Oncology Group
Verification Date July 2022

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