Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

NCT ID: NCT02883049

Last Updated: 2025-11-26

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 5949 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-02-29
• Study Completion Date: 2026-10-03

Brief Summary

This randomized phase III trial studies how well combination chemotherapy works in treating young patients with newly diagnosed B acute lymphoblastic leukemia that is likely to come back or spread, and in patients with Philadelphia chromosome (Ph)-like tyrosine kinase inhibitor (TKI) sensitive mutations. Chemotherapy drugs, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) and giving the drugs in different doses and in different combinations may kill more cancer cells.

Detailed Description

PRIMARY OBJECTIVES:

I. To determine if the administration of post-Induction age-adjusted intrathecal triple therapy (ITT) on a Modified Berlin-Frankfurt-Munster (MBFM) interim maintenance high-dose methotrexate (IMHDM) backbone will improve 5-year disease-free survival (DFS) of children with high-risk (HR) B-acute lymphoblastic leukemia (ALL) compared to age-adjusted intrathecal (IT) methotrexate (MTX). (Completed effective March 19, 2018) II. To determine, in a randomized fashion, if the cyclophosphamide + etoposide containing regimen (Experimental Arm 1) will improve the 4-year DFS of children, adolescents, and young adults with very high-risk (VHR) B-ALL compared to a modified MBFM-IMHDM regimen that contains a second IM (Control Arm). (Completed effective February 15, 2017)

SECONDARY OBJECTIVES:

I. To determine the toxicity and tolerability of post-Induction age-adjusted ITT compared to age-adjusted IT MTX in children with HR B-ALL. (Completed effective March 19, 2018) II. To determine the toxicity and tolerability of Experimental Arm 1 compared to the Control Arm in children, adolescents, and young adults with VHR B-ALL. (Completed effective February 15, 2017) III. To determine whether a single-arm, modified Induction with limited anthracycline exposure and post-Induction therapy regimen with MBFM-interim maintenance intermediate dose methotrexate (IMIDM) and reduced vincristine (vincristine sulfate)/steroid pulse frequency and enhanced supportive care in children with Down syndrome (DS) and HR B-ALL will result in a >= 65% 5-year DFS and < 10% Induction mortality.

IV. To describe the outcomes for children and young adults with Philadelphia chromosome (Ph)-like B-ALL and a predicted TKI-sensitive mutation treated with dasatinib plus MBFM-IMHDM.

V. To determine the toxicity and tolerability of MBFM-IMIDM in children with DS and HR B-ALL.

VI. To estimate overall survival (OS) rates both overall and by regimen a) for HR B-ALL and b) VHR B-ALL patients.

VII. To determine the incidence of osteonecrosis (ON), defined by magnetic resonance (MR) imaging, and to characterize the natural history of clinically silent ON in children, adolescents, and young adults 10 years of age and greater and to assess the role of drugs (i.e., asparaginase and methotrexate) in addition to corticosteroids, in the risk for development of ON. (Completed accrual July 2016) VIII. To determine if the prevalence of cognitive deficits measured by CogState, in children (ages 6 to < 13 years) with HR- and VHR B-ALL at 1 year off therapy, is significantly higher than the normative population (> 14%) in the following domains: working memory, executive function, visual motor, processing speed, and visual attention.

EXPLORATORY OBJECTIVE:

I. To determine if the reduction of minimal residual disease (MRD) from end-Induction to end-Consolidation is greater for children, adolescents, and young adults with VHR B-ALL receiving Experimental Arm 1 compared to the Control Arm. (Closed effective October 20, 2017)

OUTLINE:

INDUCTION THERAPY:

Patients without Down syndrome receive induction chemotherapy comprising cytarabine intrathecally (IT) on day 1 (and twice weekly thereafter for CNS2 patients [except for days 8 and 29]); vincristine sulfate intravenously (IV) over 1 minute on days 1, 8, 15, and 22; daunorubicin hydrochloride IV over 1-15 minutes on days 1, 8, 15, and 22; dexamethasone orally (PO) or IV twice daily (BID) on days 1-14 (patients under 10 years old) or prednisone PO or IV BID on days 1-28 (patients at least 10 years old); pegaspargase IV over 1-2 hours on day 4; and methotrexate IT on days 8 and 29 for CNS1 and CNS2 patients (plus days 15 and 22 for CNS3 patients). Treatment continues for 35 days in the absence of disease progression or unacceptable toxicity.

Participants are stratified to 1 of 3 disease groups: HR B-ALL, VHR B-ALL and PH-like B-ALL a predicted TKI-sensitive mutation.

GROUP I - HR B-ALL: Patients are randomized to 1 of 2 treatment arms. (RANDOMIZATION CLOSED 03/19/2018)

CONSOLIDATION THERAPY (C):

ARM A HR B-ALL C: Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD) on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15, and 22; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; and pegaspargase IV over 1-2 hours on days 15 and 43. Patients with continuing clinical evidence of testicular leukemia undergo radiotherapy (RT) QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

ARM B HR B-ALL C: Patients receive consolidation therapy as in Arm I HR B-ALL C. Patients also receive ITT comprising methotrexate, hydrocortisone sodium succinate, and cytarabine on days 1, 8, 15, and 22. Patients with testicular leukemia also undergo RT as in Arm I HR B-ALL C. (CLOSED 03/19/2018)

INTERIM MAINTENANCE THERAPY (IM) ARM A HR B-ALL IM: Patients receive IM therapy comprising vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; methotrexate IT on days 1 and 29; and mercaptopurine PO on days 1-56. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

ARM B HR B-ALL IM: Patients receive ITT on days 1 and 29 and IM therapy as in Arm I HR-ALL IM. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity. (CLOSED 03/19/2018)

DELAYED INTENSIFICATION THERAPY (DI):

ARM A HR B-ALL DI: Patients receive DI therapy comprising vincristine sulfate IV over 1 minute on days 1, 8, 15, 43, and 50; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; methotrexate IT on days 1, 29, and 36; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; and thioguanine PO QD on days 29-42. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

ARM B HR B-ALL DI: Patients receive ITT on days 1, 29, and 36 and DI therapy as in Arm I HR B-ALL DI. (CLOSED 03/19/2018)

MAINTENANCE THERAPY (M):

ARM A HR B-ALL M: Patients receive maintenance therapy comprising vincristine sulfate IV over 1 minute on days 1, 29, and 57; methotrexate IT on day 1 (also day 29 of courses 1-4); prednisone PO BID on days 1-5, 29-33 (may receive methylprednisolone IV if PO is not tolerated), and 57-61; mercaptopurine PO QD on days 1-84; and methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity.

ARM B HR B-ALL M: Patients receive ITT on day 1 (also day 29 of courses 1-4) and maintenance therapy as in Arm I HR B-ALL M. Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicity. (CLOSED 03/19/2018)

GROUP II: VHR B-ALL: Patients are randomized to 1 of 3 treatment arms. (RANDOMIZATION CLOSED 02/15/2017)

CONSOLIDATION THERAPY PART I: In all arms, patients receive cyclophosphamide IV over 30-60 minutes on day 1; cytarabine IV over 1-30 minutes or SC on days 1-4 and 8-11; mercaptopurine PO QD on days 1-14; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients); vincristine sulfate IV over 1 minute on days 15 and 22; and pegaspargase IV over 1-2 hours on day 15. Patients with continuing clinical evidence of testicular leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY PART II:

ARM A VHR B-ALL C (CONTROL ARM): Patients receive consolidation therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; mercaptopurine PO QD on days 29-42; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

ARM B VHR B-ALL C (EXPERIMENTAL ARM 1): Patients receive consolidation therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED 02/15/2017)

ARM C VHR B-ALL C (EXPERIMENTAL ARM 2): Patients receive clofarabine IV over 2 hours on days 29-33 and consolidation therapy as in Arm B VHR B-ALL C. (CLOSED 9/12/2014)

INTERIM MAINTENANCE THERAPY PART I: In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION THERAPY PART I: In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 8, and 15; dexamethasone PO or IV BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; methotrexate IT on day 1; and pegaspargase IV over 1-2 hours on day 4. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION THERAPY PART II:

ARM A VHR B-ALL DI (CONTROL ARM): Patients receive DI therapy comprising cyclophosphamide IV over 30-60 minutes on day 29; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; thioguanine PO QD on days 29-42; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity.

ARM B VHR B-ALL DI (EXPERIMENTAL ARM 1): Patients receive DI therapy comprising cyclophosphamide IV over 15-30 minutes on days 29-33; etoposide IV over 60-120 minutes on days 29-33; methotrexate IT on days 29 and 36; vincristine sulfate IV over 1 minute on days 43 and 50; and pegaspargase IV over 1-2 hours on day 43. Treatment continues for 28 days in the absence of disease progression or unacceptable toxicity. (CLOSED 02/15/2017)

ARM C VHR B-ALL DI (EXPERIMENTAL ARM 2): Patients receive clofarabine IV over 2 hours on days 29-33 and DI therapy as in Arm II B VHR B-ALL DI. (Closed as of 9/12/2014)

INTERIM MAINTENANCE THERAPY PART II: In all arms, patients receive vincristine sulfate IV over 1 minute and methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31, and 41; pegaspargase IV over 1-2 hours on days 2 and 22; and methotrexate IT on days 1 and 31. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

MAINENTANCE THERAPY: Patients with CNS3 disease at diagnosis undergo RT QD over 4 weeks (10 fractions total). In all arms, patients receive vincristine sulfate IV over 1 minute on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61 (may receive methylprednisolone IV if PO is not tolerated); methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78 (except on methotrexate IT days); mercaptopurine PO QD on days 1-84; methotrexate IT on day 1 (also day 29 of courses 1 and 2 for CNS patients who did not undergo RT). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities.

GROUP III: PH-LIKE PREDICTED TKI-SENSITIVE KINASE MUTATION:

CONSOLIDATION THERAPY: Patients receive dasatinib PO QD on days 1-56, cyclophosphamide IV over 30-60 minutes on days 1 and 29, cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32 and 36-39, mercaptopurine PO on days 1-14 and 29-42, methotrexate IT on days 1, 8, 15 and 22 (days 1 and 8 only for CNS3 patients), vincristine sulfate IV over 1 minute on days 15, 22, 43 and 50, and pegaspargase IV over 1-2 hours on days 15 and 43. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

INTERIM MAINTENANCE THERAPY I: Patients receive dasatinib PO QD on days 1-63, vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43, high dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, leucovorin calcium PO or IV on days 3-4, 17-18, 31-32, and 45-46, methotrexate IT on days 1 and 29, and mercaptopurine PO on days 1-56. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION THERAPY: Patients receive dasatinib PO QD on days 1-56, vincristine sulfate IV over 1 minute on days 1, 8, 15, 43, and 50, dexamethasone PO or IV on days 1-7 and 15-21, doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8 and 15, methotrexate IT on days 1, 29 and 36, pegaspargase IV over 1-2 hours on days 4 and 43, cyclophosphamide IV over 30-60 minutes day 29, cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39, and thioguanine PO on days 29-42. Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

INTERIM MAINTENANCE THERAPY II: Patients dasatinib PO QD on days 1-56, vincristine sulfate IV over 1 minute days 1, 11, 21, 31, and 41, methotrexate IV over 2-5 minutes (undiluted) or 10-15 minutes (diluted) on days 1, 11, 21, 31 and 41, methotrexate IT on days 1 and 31, and pegaspargase IV over 1-2 hours days 2 and 22.

MAINTENANCE THERAPY: Patients receive dasatinib PO QD on days 1-84, vincristine sulfate IV over 1 minute on days 1, 29 and 57, prednisone PO BID or IV 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 (omit on days when MTX [IT] is given), mercaptopurine PO on days 1-84, methotrexate IT on day 1 (also day 29 of course 1 and 2, for patients who did not receive CNS radiation). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities.

Participants with Down syndrome are assigned to DS HR B-ALL:

INDUCTION THERAPY: All patients receive cytarabine IT on day 1; vincristine sulfate IV over 1 minute on days 1 and 8, dexamethasone PO or IV BID (patients under 10 years old) or prednisone PO BID (patients at least 10 years old) on days 1-14 (may receive methylprednisolone IV if PO is not tolerated), pegaspargase IV over 1-2 hours on day 4; methotrexate IT on day 8; and leucovorin calcium PO on days 10-11. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

RAPID EARLY RESPONDERS (RER): Patients receive induction therapy comprising vincristine sulfate IV over 1 minute on days 15 and 22; dexamethasone PO BID (patients under 10 years old) or prednisone PO BID (patients at least 10 years old) on days 15-28; methotrexate IT on day 29 (also days 15 and 22 for CNS3 patients); and leucovorin calcium PO on days 31-32 (also days 17-18 and 24-25 for CNS3 patients). Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

SLOW EARLY RESPONDERS (SER): Patients receive daunorubicin hydrochloride IV over 1-15 minutes on day 15 and Induction therapy as RER patients. Treatment continues for 14 days in the absence of disease progression or unacceptable toxicity.

CONSOLIDATION THERAPY: All patients receive cyclophosphamide IV over 30-60 minutes on days 1 and 29; cytarabine IV over 1-30 minutes or SC on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO QD on days 1-14 and 29-42; vincristine sulfate IV over 1 minute on days 15, 22, 43, and 50; pegaspargase IV over 1-2 hours on days 15 and 43; methotrexate IT on days 1, 8, 15, and 22 (days 1 and 8 only for CNS3 patients); and leucovorin calcium PO on days 3-4, 10-11, 17-18, and 24-25. Patients with continuing clinical evidence of testicular leukemia undergo RT QD, 5 days a week, for approximately 2½ weeks (12 fractions total). Treatment continues for 56 days in the absence of disease progression or unacceptable toxicity.

INTERIM MAINTENANCE THERAPY: Patients receive vincristine sulfate IV over 1 minute on days 1, 15, 29, and 43; intermediate dose methotrexate IV over 24 hours on days 1, 15, 29, and 43; leucovorin calcium PO or IV on days 2-3, 17-18, 31-32, and 45-46; mercaptopurine PO QD on days 1-56; and methotrexate IT on days 1 and 29. Treatment continues for 63 days in the absence of disease progression or unacceptable toxicity.

DELAYED INTENSIFICATION THERAPY: Patients receive vincristine sulfate IV over 1 minute on days 1, 8, 15, 43, and 50; dexamethasone PO BID or IV on days 1-7 and 15-21; doxorubicin hydrochloride IV over 1-15 minutes on days 1, 8, and 15; pegaspargase IV over 1-2 hours on days 4 and 43; cyclophosphamide IV over 30-60 minutes on day 29; thioguanine PO QD on days 29-42; cytarabine IV over 1-30 minutes or SC on days 29-32 and 36-39; methotrexate IT on days 1, 29, and 36; and leucovorin calcium PO on days 3-4, 31-32 and 38-39.

MAINTENANCE THERAPY: Patients with CNS3 disease undergo RT QD, 5 days a week, for 2 weeks (10 fractions total). Patients receive vincristine sulfate IV over 1 minute on day 1; prednisone PO BID or IV on days 1-5 (may receive methylprednisolone IV if PO not tolerated); methotrexate PO on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine PO QD on days 1-84; and methotrexate IT on day 1 (also day 29 of courses 1-4 for CNS3 patients who did not undergo RT). Treatment repeats every 12 weeks for 2 years (females) or 3 years (males) in the absence of disease progression or unacceptable toxicities.

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

Conditions

B Acute Lymphoblastic Leukemia; B Acute Lymphoblastic Leukemia, BCR-ABL1-Like; Central Nervous System Leukemia; Testicular Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group I Arm B (HR B-ALL) (CLOSED 03/19/2018)

Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.

See outline for details.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IT, IV, or SC

Daunorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Dexamethasone

Intervention Type: DRUG

PO or IV

Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Hydrocortisone Sodium Succinate

Intervention Type: DRUG

Given IT

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Leucovorin Calcium

Intervention Type: DRUG

Given PO or IV

Mercaptopurine

Intervention Type: DRUG

Given PO

Methotrexate

Intervention Type: DRUG

Given IT and IV

Pegaspargase

Intervention Type: DRUG

Given IV

Prednisone

Intervention Type: DRUG

Given PO or IV

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

Thioguanine

Intervention Type: DRUG

Given PO

Vincristine Sulfate

Intervention Type: DRUG

Given IV

Group II Arm A (VHR B-ALL - Control Arm)

Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.

See outline for details.

Group Type: ACTIVE_COMPARATOR

Cyclophosphamide

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IT, IV, or SC

Daunorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Dexamethasone

Intervention Type: DRUG

PO or IV

Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Leucovorin Calcium

Intervention Type: DRUG

Given PO or IV

Mercaptopurine

Intervention Type: DRUG

Given PO

Methotrexate

Intervention Type: DRUG

Given IT and IV

Pegaspargase

Intervention Type: DRUG

Given IV

Prednisone

Intervention Type: DRUG

Given PO or IV

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

Thioguanine

Intervention Type: DRUG

Given PO

Vincristine Sulfate

Intervention Type: DRUG

Given IV

Group II Arm B (VHR B-ALL - Exp Arm1) (CLOSED 02/15/2017)

Patients receive consolidation, interim maintenance, delayed intensification and maintenance therapies.

See outline for details.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IT, IV, or SC

Daunorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Etoposide

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Leucovorin Calcium

Intervention Type: DRUG

Given PO or IV

Mercaptopurine

Intervention Type: DRUG

Given PO

Methotrexate

Intervention Type: DRUG

Given IT and IV

Pegaspargase

Intervention Type: DRUG

Given IV

Prednisone

Intervention Type: DRUG

Given PO or IV

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

Vincristine Sulfate

Intervention Type: DRUG

Given IV

Group II Arm C (VHR B-ALL - Exp Arm 2) (CLOSED 09/12/2014)

Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.

See outline for details.

Group Type: EXPERIMENTAL

Clofarabine

Intervention Type: DRUG

Given IV

Cyclophosphamide

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IT, IV, or SC

Daunorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Dexamethasone

Intervention Type: DRUG

PO or IV

Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Etoposide

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Leucovorin Calcium

Intervention Type: DRUG

Given PO or IV

Mercaptopurine

Intervention Type: DRUG

Given PO

Methotrexate

Intervention Type: DRUG

Given IT and IV

Pegaspargase

Intervention Type: DRUG

Given IV

Prednisone

Intervention Type: DRUG

Given PO or IV

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

Vincristine Sulfate

Intervention Type: DRUG

Given IV

Group III PH-like predicted TKI-sensitive kinase mutation

Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.

See outline for details.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IT, IV, or SC

Dasatinib

Intervention Type: DRUG

Given PO

Daunorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Dexamethasone

Intervention Type: DRUG

PO or IV

Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Leucovorin Calcium

Intervention Type: DRUG

Given PO or IV

Mercaptopurine

Intervention Type: DRUG

Given PO

Methotrexate

Intervention Type: DRUG

Given IT and IV

Pegaspargase

Intervention Type: DRUG

Given IV

Prednisone

Intervention Type: DRUG

Given PO or IV

Vincristine Sulfate

Intervention Type: DRUG

Given IV

DS HR B-ALL (RER)

Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.

See outline for details.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IT, IV, or SC

Dexamethasone

Intervention Type: DRUG

PO or IV

Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Leucovorin Calcium

Intervention Type: DRUG

Given PO or IV

Mercaptopurine

Intervention Type: DRUG

Given PO

Methotrexate

Intervention Type: DRUG

Given IT and IV

Pegaspargase

Intervention Type: DRUG

Given IV

Prednisone

Intervention Type: DRUG

Given PO or IV

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

Thioguanine

Intervention Type: DRUG

Given PO

Vincristine Sulfate

Intervention Type: DRUG

Given IV

DS HR B-ALL (SER)

Patients receive induction, consolidation, interim maintenance, delayed intensification, interim maintenance and maintenance therapies.

See outline for details.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IT, IV, or SC

Daunorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Dexamethasone

Intervention Type: DRUG

PO or IV

Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Leucovorin Calcium

Intervention Type: DRUG

Given PO or IV

Mercaptopurine

Intervention Type: DRUG

Given PO

Methotrexate

Intervention Type: DRUG

Given IT and IV

Pegaspargase

Intervention Type: DRUG

Given IV

Prednisone

Intervention Type: DRUG

Given PO or IV

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

Thioguanine

Intervention Type: DRUG

Given PO

Vincristine Sulfate

Intervention Type: DRUG

Given IV

Group I Arm A (HR B-ALL)

Patients receive induction, consolidation, interim maintenance, delayed intensification and maintenance therapies.

See outline for details.

Group Type: EXPERIMENTAL

Cyclophosphamide

Intervention Type: DRUG

Given IV

Cytarabine

Intervention Type: DRUG

Given IT, IV, or SC

Daunorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Dexamethasone

Intervention Type: DRUG

PO or IV

Doxorubicin Hydrochloride

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Leucovorin Calcium

Intervention Type: DRUG

Given PO or IV

Mercaptopurine

Intervention Type: DRUG

Given PO

Methotrexate

Intervention Type: DRUG

Given IT and IV

Pegaspargase

Intervention Type: DRUG

Given IV

Prednisone

Intervention Type: DRUG

Given PO or IV

Radiation Therapy

Intervention Type: RADIATION

Undergo radiation therapy

Thioguanine

Intervention Type: DRUG

Given PO

Vincristine Sulfate

Intervention Type: DRUG

Given IV

Interventions

Clofarabine

Given IV

Intervention Type: DRUG

Cyclophosphamide

Given IV

Intervention Type: DRUG

Cytarabine

Given IT, IV, or SC

Intervention Type: DRUG

Dasatinib

Given PO

Intervention Type: DRUG

Daunorubicin Hydrochloride

Given IV

Intervention Type: DRUG

Dexamethasone

PO or IV

Intervention Type: DRUG

Doxorubicin Hydrochloride

Given IV

Intervention Type: DRUG

Etoposide

Given IV

Intervention Type: DRUG

Hydrocortisone Sodium Succinate

Given IT

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Leucovorin Calcium

Given PO or IV

Intervention Type: DRUG

Mercaptopurine

Given PO

Intervention Type: DRUG

Methotrexate

Given IT and IV

Intervention Type: DRUG

Pegaspargase

Given IV

Intervention Type: DRUG

Prednisone

Given PO or IV

Intervention Type: DRUG

Radiation Therapy

Undergo radiation therapy

Intervention Type: RADIATION

Thioguanine

Given PO

Intervention Type: DRUG

Vincristine Sulfate

Given IV

Intervention Type: DRUG

Other Intervention Names

Clofarex; Clolar; (-)-Cyclophosphamide; 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate; Asta B 518; B 518; B-518; B518; 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; WR- 138719; WR-138719; WR138719; .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; BMS 354825; BMS-354825; BMS354825; Dasatinib Hydrate; Dasatinib Monohydrate; Sprycel; Cerubidin; Cerubidine; Cloridrato de Daunorubicina; Daunoblastin; Daunoblastina; Daunoblastine; Daunomycin Hydrochloride; Daunomycin, hydrochloride; Daunorubicin.HCl; Daunorubicini Hydrochloridum; FI-6339; Ondena; RP-13057; Rubidomycin Hydrochloride; Rubilem; 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; Hemady; Hexadecadrol; Hexadrol; LenaDex; Lokalison-F; Loverine; Methylfluorprednisolone; Millicorten; Mymethasone; Orgadrone; Spersadex; TaperDex; Visumetazone; ZoDex; 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; FI106; hydroxydaunorubicin; Rubex; Demethyl Epipodophyllotoxin Ethylidine Glucoside; EPEG; Lastet; Toposar; Vepesid; VP 16; VP 16-213; VP 16213; VP-16; VP-16-213; VP-16213; VP16; VP16213; (11beta)-21-(3-Carboxy-1-oxopropyl)-11,17-dihydroxypregn-4-ene-3,20-dione, Monosodium Salt; A-Hydrocort; Buccalsone; Corlan; Cortisol Sodium Succinate; Cortop; Efcortelan; Emergent-EZ; Flebocortid; Hidroc Clora; Hycorace; Hydro-Adreson; Hydrocort; Hydrocortisone 21-Sodium Succinate; Hydrocortisone Na Succinate; Kinogen; Nordicort; Nositrol; Sinsurrene; Sodium hydrocortisone succinate; Solu-Cortef; Solu-Glyc; 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; 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; Abitrexate; Alpha-Methopterin; Amethopterin; Brimexate; CL 14377; CL-14377; Emtexate; Emthexat; Emthexate; Farmitrexat; Fauldexato; Folex; Folex PFS; Jylamvo; 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; 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; .delta.1-Cortisone; 1, 2-Dehydrocortisone; Adasone; Cortancyl; Dacortin; DeCortin; Decortisyl; Decorton; Delta 1-Cortisone; Delta-Dome; Deltacortene; Deltacortisone; Deltadehydrocortisone; Deltasone; Deltison; Deltra; Econosone; Lisacort; Meprosona-F; Metacortandracin; Meticorten; Ofisolona; Orasone; Panafcort; Panasol-S; Paracort; Perrigo Prednisone; PRED; Predicor; Predicorten; Prednicen-M; Prednicort; Prednidib; Prednilonga; Predniment; Prednisone Intensol; Prednisonum; Prednitone; Promifen; Rayos; Servisone; SK-Prednisone; Cancer Radiotherapy; Energy Type; ENERGY_TYPE; Irradiate; Irradiated; Irradiation; Radiation; Radiation Therapy, NOS; Radiotherapeutics; Radiotherapy; RT; Therapy, Radiation; 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; Kyocristine; Leurocristine Sulfate; Leurocristine, sulfate; Oncovin; Vincasar; Vincosid; Vincrex; Vincristine, sulfate

Eligibility Criteria

Inclusion Criteria

• Patients must be enrolled on APEC14B1 and consented to Eligibility Screening on the Part A consent form prior to enrollment on AALL1131
• White Blood Cell Count (WBC) Criteria

• Age 1-9.99 years: WBC >= 50 000/uL
• Age 10-30.99 years: Any WBC
• Age 1-30.99 years: Any WBC with:

• Testicular leukemia
• CNS leukemia (CNS3)
• Steroid pretreatment
• Patients must have newly diagnosed B lymphoblastic leukemia (2008 World Health Organization [WHO] classification) (also termed B-precursor acute lymphoblastic leukemia); patients with Down syndrome are also eligible
• Organ function requirements for patients with Ph-like ALL and a predicted TKI-sensitive mutation: patients identified as Ph-like with a TKI-sensitive kinase mutation must have assessment of organ function performed within 3 days of study entry onto the dasatinib arm of AALL1131
• Creatinine clearance or radioisotope glomerular filtration rate (GFR) > 70mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

• Age: Maximum Serum Creatinine (mg/dL)
• 1 to < 6 months: 0.4 (male) 0.4 (female)
• 6 months to < 1 year: 0.5 (male) 0.5 (female)
• 1 to < 2 years: 0.6 (male) 0.6 (female)
• 2 < 6 years: 0.8 (male) 0.8 (female)
• 6 to < 10 years: 1.0 (male) 1.0 (female)
• 10 to < 13 years: 1.2 (male) 1.2 (female)
• 13 to < 16 years: 1.5 (male) 1.4 (female)
• > 16 years: 1.7 (male) 1.4 (female)
• Direct bilirubin =< 3 x upper limit of normal (ULN) for age, and
• Serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =< 10 x upper limit of normal (ULN) for age
• Shortening fraction >= 27% by echocardiogram, or ejection fraction >= 50% by gated radionuclide study

• Patients must have an electrocardiogram (EKG) fewer than 6 days prior to enrollment on the dasatinib arm; patients who have had cardiac assessments by echocardiogram or radionuclide scan at the beginning of induction do not need to have these repeated prior to study entry; correct QT interval (QTc) < 450 msec on baseline electrocardiogram as measured by the Friderica or Bazett formula
• No major conduction abnormality (unless a cardiac pacemaker is present)
• No evidence of dyspnea at rest, no exercise intolerance, and a pulse oximetry > 94% at sea level if there is clinical indication for determination
• Patients with seizure disorder may be enrolled if on anticonvulsants and well controlled; however, drugs that induce CYP3A4/5 (carbamazepine, oxcarbazepine, phenytoin, primidone, phenobarbital) should be avoided
• Eligibility criteria for the Longitudinal, Computerized Assessment of Neurocognitive Functioning study

• Patients must be aged 6 to 13 years at time of B-ALL diagnosis, enrolled on AALL1131
• Patients must be English-, French- or Spanish-speaking (languages in which the assessment is available)
• Patients must have no known history of neurodevelopmental disorder prior to diagnosis of B-ALL (e.g., Down syndrome, Fragile X, William's Syndrome, mental retardation)
• Patients must have no significant visual impairment that would prevent computer use and recognition of the visual test stimuli
• Eligibility criteria for the National Cancer Institute (NCI) standard risk patients from AALL0932 enrolling on this study at the end of Induction
• Effective March 19, 2018, patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 or the HR B-ALL stratum of this study at the end of Induction:

• Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day 8 peripheral blood (PB) minimal residual disease (MRD) >= 1% and day 29 bone marrow (BM) MRD < 0.01%
• With favorable cytogenetics (ETV6-RUNX1 or double trisomies 4+10), with any day 8 PB MRD and day 29 BM MRD >= 0.01%
• Both NCI standard risk (SR) and HR patients without Down syndrome and with testicular disease at diagnosis, who do not meet other VHR criteria
• Effective Amendment 6, patients enrolled on AALL0932, without Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 or the VHR stratum of AALL1131:

• Intrachromosomal amplification of chromosome 21 (iAMP21)
• Mixed-lineage leukemia (MLL) rearrangement
• Hypodiploidy (n < 44 chromosomes and/or a deoxyribonucleic acid [DNA] index < 0.81)
• Induction failure (M3 BM at day 29)
• Without favorable cytogenetics (no ETV6-RUNX1 or double trisomies 4+10), with day 29 BM MRD >= 0.01%
• Patients enrolled on AALL0932, with Down syndrome, meeting the following criteria will NOT be eligible to continue on AALL0932 but WILL BE eligible to enroll on the DS HR B-ALL stratum of this study at the end of Induction:

• Day 29 MRD >= 0.01%
• MLL rearrangement
• Hypodiploidy (n < 45 chromosomes and/or DNA index < 0.81)
• DS HR B-ALL patients initially enrolled on AALL0932 or this study who have Induction failure (M3 BM day 29) or Philadelphia chromosome (BCR-ABL1) will not be eligible for post-Induction therapy on either trial (AALL0932 or AALL1131)
• All patients and/or their parents or legal guardians must sign a written informed consent
• All institutional, Food and Drug Administration (FDA), and NCI requirements for human studies must be met

Exclusion Criteria

• With the exception of steroid pretreatment or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or any cancer diagnosed prior to the initiation of protocol therapy on AALL1131; patients cannot have secondary B-ALL that developed after treatment of a prior malignancy with cytotoxic chemotherapy; patients receiving prior steroid therapy may be eligible for AALL1131
• Patients with BCR-ABL1 fusion are not eligible for post-induction therapy on this study but may be eligible to enroll in a successor Children's Oncology Group (COG) Philadelphia positive (Ph+) ALL trial by day 15 Induction
• DS HR B-ALL patients with Induction failure or BCR-ABL1
• Female patients who are pregnant are ineligible since fetal toxicities and teratogenic effects have been noted for several of the study drugs
• Lactating females are not eligible unless they have agreed not to breastfeed their infant
• Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
• Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

• Minimum Eligible Age: 1 Year
• Maximum Eligible Age: 31 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael J Burke

Role: PRINCIPAL_INVESTIGATOR

Children's Oncology Group

Locations

Children's Hospital of Alabama

Birmingham, Alabama, United States

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, United States

USA Health Strada Patient Care Center

Mobile, Alabama, United States

Providence Alaska Medical Center

Anchorage, Alaska, United States

Banner Children's at Desert

Mesa, Arizona, United States

Phoenix Childrens Hospital

Phoenix, Arizona, United States

Banner University Medical Center - Tucson

Tucson, Arizona, United States

Arkansas Children's Hospital

Little Rock, Arkansas, United States

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Kaiser Permanente Downey Medical Center

Downey, California, United States

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Loma Linda University Medical Center

Loma Linda, California, United States

Miller Children's and Women's Hospital Long Beach

Long Beach, California, United States

Children's Hospital Los Angeles

Los Angeles, California, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

Mattel Children's Hospital UCLA

Los Angeles, California, United States

Valley Children's Hospital

Madera, California, United States

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

Kaiser Permanente-Oakland

Oakland, California, United States

Children's Hospital of Orange County

Orange, California, United States

Lucile Packard Children's Hospital Stanford University

Palo Alto, California, United States

Sutter Medical Center Sacramento

Sacramento, California, United States

University of California Davis Comprehensive Cancer Center

Sacramento, California, United States

Rady Children's Hospital - San Diego

San Diego, California, United States

Naval Medical Center -San Diego

San Diego, California, United States

UCSF Medical Center-Parnassus

San Francisco, California, United States

UCSF Medical Center-Mission Bay

San Francisco, California, United States

Santa Barbara Cottage Hospital

Santa Barbara, California, United States

Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center

Torrance, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center

Denver, Colorado, United States

Connecticut Children's Medical Center

Hartford, Connecticut, United States

Yale University

New Haven, Connecticut, United States

Alfred I duPont Hospital for Children

Wilmington, Delaware, United States

MedStar Georgetown University Hospital

Washington D.C., District of Columbia, United States

Children's National Medical Center

Washington D.C., District of Columbia, United States

Broward Health Medical Center

Fort Lauderdale, Florida, United States

Lee Memorial Health System

Fort Myers, Florida, United States

Golisano Children's Hospital of Southwest Florida

Fort Myers, Florida, United States

UF Health Cancer Institute - Gainesville

Gainesville, Florida, United States

Memorial Regional Hospital/Joe DiMaggio Children's Hospital

Hollywood, Florida, United States

Nemours Children's Clinic-Jacksonville

Jacksonville, Florida, United States

Palms West Radiation Therapy

Loxahatchee Groves, Florida, United States

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, United States

Nicklaus Children's Hospital

Miami, Florida, United States

Miami Cancer Institute

Miami, Florida, United States

AdventHealth Orlando

Orlando, Florida, United States

Arnold Palmer Hospital for Children

Orlando, Florida, United States

Nemours Children's Clinic - Orlando

Orlando, Florida, United States

Orlando Health Cancer Institute

Orlando, Florida, United States

Nemours Children's Hospital

Orlando, Florida, United States

Nemours Children's Clinic - Pensacola

Pensacola, Florida, United States

Johns Hopkins All Children's Hospital

St. Petersburg, Florida, United States

Tampa General Hospital

Tampa, Florida, United States

Saint Joseph's Hospital/Children's Hospital-Tampa

Tampa, Florida, United States

Saint Mary's Medical Center

West Palm Beach, Florida, United States

Children's Healthcare of Atlanta - Arthur M Blank Hospital

Atlanta, Georgia, United States

Augusta University Medical Center

Augusta, Georgia, United States

Memorial Health University Medical Center

Savannah, Georgia, United States

University of Hawaii Cancer Center

Honolulu, Hawaii, United States

Kapiolani Medical Center for Women and Children

Honolulu, Hawaii, United States

Tripler Army Medical Center

Honolulu, Hawaii, United States

Saint Luke's Cancer Institute - Boise

Boise, Idaho, United States

Lurie Children's Hospital-Chicago

Chicago, Illinois, United States

University of Illinois

Chicago, Illinois, United States

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, United States

Loyola University Medical Center

Maywood, Illinois, United States

Advocate Children's Hospital-Oak Lawn

Oak Lawn, Illinois, United States

Advocate Children's Hospital-Park Ridge

Park Ridge, Illinois, United States

Advocate Lutheran General Hospital

Park Ridge, Illinois, United States

Saint Jude Midwest Affiliate

Peoria, Illinois, United States

Southern Illinois University School of Medicine

Springfield, Illinois, United States

Riley Hospital for Children

Indianapolis, Indiana, United States

Ascension Saint Vincent Indianapolis Hospital

Indianapolis, Indiana, United States

Blank Children's Hospital

Des Moines, Iowa, United States

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, United States

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, United States

Norton Children's Hospital

Louisville, Kentucky, United States

Tulane University School of Medicine

New Orleans, Louisiana, United States

Children's Hospital New Orleans

New Orleans, Louisiana, United States

Ochsner Medical Center Jefferson

New Orleans, Louisiana, United States

Eastern Maine Medical Center

Bangor, Maine, United States

Maine Children's Cancer Program

Scarborough, Maine, United States

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, United States

Sinai Hospital of Baltimore

Baltimore, Maryland, United States

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, United States

Walter Reed National Military Medical Center

Bethesda, Maryland, United States

Tufts Children's Hospital

Boston, Massachusetts, United States

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, United States

Baystate Medical Center

Springfield, Massachusetts, United States

UMass Memorial Medical Center - University Campus

Worcester, Massachusetts, United States

C S Mott Children's Hospital

Ann Arbor, Michigan, United States

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, United States

Henry Ford Health Saint John Hospital

Detroit, Michigan, United States

Michigan State University

East Lansing, Michigan, United States

Hurley Medical Center

Flint, Michigan, United States

Corewell Health Grand Rapids Hospitals - Helen DeVos Children's Hospital

Grand Rapids, Michigan, United States

Bronson Methodist Hospital

Kalamazoo, Michigan, United States

Corewell Health Children's

Royal Oak, Michigan, United States

Corewell Health William Beaumont University Hospital

Royal Oak, Michigan, United States

Children's Hospitals and Clinics of Minnesota - Minneapolis

Minneapolis, Minnesota, United States

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, United States

Mayo Clinic in Rochester

Rochester, Minnesota, United States

University of Mississippi Medical Center

Jackson, Mississippi, United States

University of Missouri Children's Hospital

Columbia, Missouri, United States

Children's Mercy Hospitals and Clinics

Kansas City, Missouri, United States

Cardinal Glennon Children's Medical Center

St Louis, Missouri, United States

Washington University School of Medicine

St Louis, Missouri, United States

Mercy Hospital Saint Louis

St Louis, Missouri, United States

Children's Hospital and Medical Center of Omaha

Omaha, Nebraska, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

University Medical Center of Southern Nevada

Las Vegas, Nevada, United States

Sunrise Hospital and Medical Center

Las Vegas, Nevada, United States

Alliance for Childhood Diseases/Cure 4 the Kids Foundation

Las Vegas, Nevada, United States

Summerlin Hospital Medical Center

Las Vegas, Nevada, United States

Dartmouth Hitchcock Medical Center/Dartmouth Cancer Center

Lebanon, New Hampshire, United States

Hackensack University Medical Center

Hackensack, New Jersey, United States

Saint Barnabas Medical Center

Livingston, New Jersey, United States

Morristown Medical Center

Morristown, New Jersey, United States

Saint Peter's University Hospital

New Brunswick, New Jersey, United States

Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital

New Brunswick, New Jersey, United States

Newark Beth Israel Medical Center

Newark, New Jersey, United States

Saint Joseph's Regional Medical Center

Paterson, New Jersey, United States

Overlook Hospital

Summit, New Jersey, United States

University of New Mexico Cancer Center

Albuquerque, New Mexico, United States

Albany Medical Center

Albany, New York, United States

Roswell Park Cancer Institute

Buffalo, New York, United States

NYU Langone Hospital - Long Island

Mineola, New York, United States

The Steven and Alexandra Cohen Children's Medical Center of New York

New Hyde Park, New York, United States

Laura and Isaac Perlmutter Cancer Center at NYU Langone

New York, New York, United States

Mount Sinai Hospital

New York, New York, United States

NYP/Weill Cornell Medical Center

New York, New York, United States

University of Rochester

Rochester, New York, United States

Stony Brook University Medical Center

Stony Brook, New York, United States

State University of New York Upstate Medical University

Syracuse, New York, United States

Montefiore Medical Center - Moses Campus

The Bronx, New York, United States

New York Medical College

Valhalla, New York, United States

Mission Hospital

Asheville, North Carolina, United States

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, United States

Novant Health Presbyterian Medical Center

Charlotte, North Carolina, United States

Duke University Medical Center

Durham, North Carolina, United States

East Carolina University

Greenville, North Carolina, United States

Wake Forest University Health Sciences

Winston-Salem, North Carolina, United States

Sanford Broadway Medical Center

Fargo, North Dakota, United States

Children's Hospital Medical Center of Akron

Akron, Ohio, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Rainbow Babies and Childrens Hospital

Cleveland, Ohio, United States

Cleveland Clinic Foundation

Cleveland, Ohio, United States

Nationwide Children's Hospital

Columbus, Ohio, United States

Dayton Children's Hospital

Dayton, Ohio, United States

ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital

Toledo, Ohio, United States

Mercy Children's Hospital

Toledo, Ohio, United States

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Natalie Warren Bryant Cancer Center at Saint Francis

Tulsa, Oklahoma, United States

Legacy Emanuel Children's Hospital

Portland, Oregon, United States

Oregon Health and Science University

Portland, Oregon, United States

Lehigh Valley Hospital-Cedar Crest

Allentown, Pennsylvania, United States

Lehigh Valley Hospital - Muhlenberg

Bethlehem, Pennsylvania, United States

Geisinger Medical Center

Danville, Pennsylvania, United States

Penn State Children's Hospital

Hershey, Pennsylvania, United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Saint Christopher's Hospital for Children

Philadelphia, Pennsylvania, United States

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, United States

Rhode Island Hospital

Providence, Rhode Island, United States

Medical University of South Carolina

Charleston, South Carolina, United States

Prisma Health Richland Hospital

Columbia, South Carolina, United States

BI-LO Charities Children's Cancer Center

Greenville, South Carolina, United States

Greenville Cancer Treatment Center

Greenville, South Carolina, United States

Sanford USD Medical Center - Sioux Falls

Sioux Falls, South Dakota, United States

T C Thompson Children's Hospital

Chattanooga, Tennessee, United States

East Tennessee Childrens Hospital

Knoxville, Tennessee, United States

Saint Jude Children's Research Hospital

Memphis, Tennessee, United States

The Children's Hospital at TriStar Centennial

Nashville, Tennessee, United States

Vanderbilt University/Ingram Cancer Center

Nashville, Tennessee, United States

Texas Tech University Health Sciences Center-Amarillo

Amarillo, Texas, United States

Dell Children's Medical Center of Central Texas

Austin, Texas, United States

Driscoll Children's Hospital

Corpus Christi, Texas, United States

Medical City Dallas Hospital

Dallas, Texas, United States

UT Southwestern/Simmons Cancer Center-Dallas

Dallas, Texas, United States

El Paso Children's Hospital

El Paso, Texas, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center

Houston, Texas, United States

M D Anderson Cancer Center

Houston, Texas, United States

Covenant Children's Hospital

Lubbock, Texas, United States

UMC Cancer Center / UMC Health System

Lubbock, Texas, United States

Vannie Cook Children's Clinic

McAllen, Texas, United States

Children's Hospital of San Antonio

San Antonio, Texas, United States

Methodist Children's Hospital of South Texas

San Antonio, Texas, United States

University of Texas Health Science Center at San Antonio

San Antonio, Texas, United States

Scott and White Memorial Hospital

Temple, Texas, United States

Primary Children's Hospital

Salt Lake City, Utah, United States

University of Vermont and State Agricultural College

Burlington, Vermont, United States

University of Virginia Cancer Center

Charlottesville, Virginia, United States

Inova Fairfax Hospital

Falls Church, Virginia, United States

Children's Hospital of The King's Daughters

Norfolk, Virginia, United States

Naval Medical Center - Portsmouth

Portsmouth, Virginia, United States

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, United States

Carilion Children's

Roanoke, Virginia, United States

Seattle Children's Hospital

Seattle, Washington, United States

Providence Sacred Heart Medical Center and Children's Hospital

Spokane, Washington, United States

Mary Bridge Children's Hospital and Health Center

Tacoma, Washington, United States

Madigan Army Medical Center

Tacoma, Washington, United States

West Virginia University Charleston Division

Charleston, West Virginia, United States

West Virginia University Healthcare

Morgantown, West Virginia, United States

Saint Vincent Hospital Cancer Center Green Bay

Green Bay, Wisconsin, United States

University of Wisconsin Carbone Cancer Center - University Hospital

Madison, Wisconsin, United States

Marshfield Medical Center-Marshfield

Marshfield, Wisconsin, United States

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, United States

John Hunter Children's Hospital

Hunter Regional Mail Centre, New South Wales, Australia

Royal Brisbane and Women's Hospital

Herston, Queensland, Australia

Royal Children's Hospital-Brisbane

Herston, Queensland, Australia

Queensland Children's Hospital

South Brisbane, Queensland, Australia

Women's and Children's Hospital-Adelaide

North Adelaide, South Australia, Australia

Monash Medical Center-Clayton Campus

Clayton, Victoria, Australia

Royal Children's Hospital

Parkville, Victoria, Australia

Princess Margaret Hospital for Children

Perth, Western Australia, Australia

Perth Children's Hospital

Perth, Western Australia, Australia

Alberta Children's Hospital

Calgary, Alberta, Canada

University of Alberta Hospital

Edmonton, Alberta, Canada

British Columbia Children's Hospital

Vancouver, British Columbia, Canada

CancerCare Manitoba

Winnipeg, Manitoba, Canada

Janeway Child Health Centre

St. John's, Newfoundland and Labrador, Canada

IWK Health Centre

Halifax, Nova Scotia, Canada

McMaster Children's Hospital at Hamilton Health Sciences

Hamilton, Ontario, Canada

Kingston Health Sciences Centre

Kingston, Ontario, Canada

Children's Hospital

London, Ontario, Canada

Children's Hospital of Eastern Ontario

Ottawa, Ontario, Canada

Hospital for Sick Children

Toronto, Ontario, Canada

The Montreal Children's Hospital of the MUHC

Montreal, Quebec, Canada

Allan Blair Cancer Centre

Regina, Saskatchewan, Canada

Saskatoon Cancer Centre

Saskatoon, Saskatchewan, Canada

Our Lady's Children's Hospital

Dublin, Co Dublin, Ireland

Starship Children's Hospital

Grafton, Auckland, New Zealand

Christchurch Hospital

Christchurch, , New Zealand

San Jorge Children's Hospital

San Juan, , Puerto Rico

University Pediatric Hospital

San Juan, , Puerto Rico

Swiss Pediatric Oncology Group - Geneva

Geneva, , Switzerland

Swiss Pediatric Oncology Group - Lausanne

Lausanne, , Switzerland

Countries

United States; Australia; Canada; Ireland; New Zealand; Puerto Rico; Switzerland

References

Chang TC, Chen W, Qu C, Cheng Z, Hedges D, Elsayed A, Pounds SB, Shago M, Rabin KR, Raetz EA, Devidas M, Cheng C, Angiolillo A, Baviskar P, Borowitz M, Burke MJ, Carroll A, Carroll WL, Chen IM, Harvey R, Heerema N, Iacobucci I, Wang JR, Jeha S, Larsen E, Mattano L, Maloney K, Pui CH, Ramirez NC, Salzer W, Willman C, Winick N, Wood B, Hunger SP, Wu G, Mullighan CG, Loh ML. Genomic Determinants of Outcome in Acute Lymphoblastic Leukemia. J Clin Oncol. 2024 Oct 10;42(29):3491-3503. doi: 10.1200/JCO.23.02238. Epub 2024 Aug 9.

Reference Type: DERIVED

PMID: 39121442 (View on PubMed)

Rabin KR, Devidas M, Chen Z, Ji L, Kairalla J, Hitzler JK, Yang JJ, Carroll AJ, Heerema NA, Borowitz MJ, Wood BL, Roberts KG, Mullighan CG, Harvey RC, Chen IM, Willman CL, Reshmi SC, Gastier-Foster JM, Bhojwani D, Rheingold SR, Maloney KW, Mattano LA, Larsen EC, Schore RJ, Burke MJ, Salzer WL, Winick NJ, Carroll WL, Raetz EA, Loh ML, Hunger SP, Angiolillo AL. Outcomes in Children, Adolescents, and Young Adults With Down Syndrome and ALL: A Report From the Children's Oncology Group. J Clin Oncol. 2024 Jan 10;42(2):218-227. doi: 10.1200/JCO.23.00389. Epub 2023 Oct 27.

Reference Type: DERIVED

PMID: 37890117 (View on PubMed)

Salzer WL, Burke MJ, Devidas M, Dai Y, Hardy KK, Kairalla JA, Gore L, Hilden JM, Larsen E, Rabin KR, Zweidler-McKay PA, Borowitz MJ, Wood B, Heerema NA, Carroll AJ, Winick N, Carroll WL, Raetz EA, Loh ML, Hunger SP. Impact of Intrathecal Triple Therapy Versus Intrathecal Methotrexate on Disease-Free Survival for High-Risk B-Lymphoblastic Leukemia: Children's Oncology Group Study AALL1131. J Clin Oncol. 2020 Aug 10;38(23):2628-2638. doi: 10.1200/JCO.19.02892. Epub 2020 Jun 4.

Reference Type: DERIVED

PMID: 32496902 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

https://nctn-data-archive.nci.nih.gov/

Select individual patient-level data from this trial can be requested from the NCTN/NCORP Data Archive.

Other Identifiers

NCI-2011-03797

Identifier Type: REGISTRY

Identifier Source: secondary_id

S12-01254

Identifier Type: -

Identifier Source: secondary_id

CDR0000706370

Identifier Type: -

Identifier Source: secondary_id

COG-AALL1131

Identifier Type: -

Identifier Source: secondary_id

AALL1131

Identifier Type: OTHER

Identifier Source: secondary_id

AALL1131

Identifier Type: OTHER

Identifier Source: secondary_id

U10CA098543

Identifier Type: NIH

Identifier Source: secondary_id

View Link

U10CA180886

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NCI-2011-03797

Identifier Type: -

Identifier Source: org_study_id

NCT01406756

Identifier Type: -

Identifier Source: nct_alias