Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia

Basic Trial Information

Objectives

1. Compare the efficacy and toxicity of short methotrexate infusion vs longer infusion in patients with low-risk acute lymphoblastic leukemia.
2. Compare the efficacy of these regimens of methotrexate, with or without multidrug intensification, in these patients.

Entry Criteria

Disease Characteristics:

• Diagnosis of B-cell precursor acute lymphoblastic leukemia
  • Registered on POG-9900 Classification Study

• Registered within 7 days of documenting complete response (CR) after induction therapy on day 29 or, if 2 more weeks of induction are required, within 7 days of CR determination

• Classified as low-risk:
  • WBC less than 50,000/mm³
  • Age 1 to 9
  • No adverse translocations [E2A-PBX1, t(1;19) or BCR/ABL, t(9;22); and MLL rearrangements]
  • No CNS 3 disease (CSF WBC at least 5/mm³ with blasts present)
  • No testicular disease
  • At least one of the following present:
    • TEL/AML1, t(12;21)
    • Simultaneous trisomy of chromosomes 4 and 10

Prior/Concurrent Therapy:

Biologic therapy

• Not specified

Chemotherapy

• Not specified

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified

Patient Characteristics:

Age:

• 1 to 9

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• See Disease Characteristics

Hepatic:

• Not specified

Renal:

• Not specified

Other:

• Not pregnant or nursing
• Fertile patients must use effective contraception

Expected Enrollment

A total 902 patients will be accrued for this study within 3.22 years.

Outcomes

Disease-free survival at multiple time points

Outline

This is a randomized, multicenter study. Patients are stratified according to genetics (stratum 1: trisomy 4/10 but not TEL/AML1 vs stratum 2: TEL/AML1 with or without trisomy 4/10).

All patients receive induction therapy (weeks 1-4) on another protocol (POG-9900).

Stratum 1

• Consolidation therapy begins on week 5. Patients are randomized to arm I or II.
  • Arm I: Patients receive methotrexate (MTX) IV over 24 hours on day 1 and oral leucovorin calcium (CF) every 6 hours for 3 doses beginning 42 hours after initiation of MTX infusion during weeks 7, 10, 13, 16, and 19.

  • Arm II: Patients receive MTX IV over 4 hours on day 1 and oral CF as in arm I during weeks 7, 10, 13, 16, and 19.

• Patients in arms I and II also receive MTX intrathecally (IT) on weeks 7, 10, 13, 16, 19, and 22; oral mercaptopurine (6-MP) daily on weeks 5-24; oral dexamethasone (DM) twice daily on days 1-7 of weeks 8 and 17; and vincristine (VCR) IV on day 1 of weeks 8, 9, 17, and 18.

Stratum 2

• Consolidation therapy begins on week 5 and delayed intensification therapy begins on week 16. Patients are randomized to delayed intensification or no delayed intensification. Patients randomized to no delayed intensification are then randomized to consolidation therapy on arm I or II. Patients randomized to delayed intensification are then randomized to arm III or IV. Patients with trisomy 4/10 are not randomized to arms III and IV.
  • Arm III: Patients receive MTX IV and CF as in arm I on weeks 7, 10, 13, 24, 27, and 30.

  • Arm IV: Patients receive MTX IV and CF as in arm II on weeks 7, 10, 13, 24, 27, and 30.

• Patients in arms III and IV also receive oral 6-MP daily on weeks 5-13 and then beginning on week 24 and continuing until the end of consolidation; MTX IT on weeks 7, 10, 13, 16, 20, 21, and 30; oral DM twice daily on days 1-7 of weeks 8, 16-18, and 28; VCR IV on day 1 of weeks 8, 9, 16-18, 28, and 29; pegaspargase intramuscularly on week 16; daunorubicin IV on day 1 of weeks 16-18; cyclophosphamide IV on day 1 of week 20; cytarabine IV or subcutaneously on days 2-5 of weeks 20 and 21; and oral thioguanine daily on days 1-14 of weeks 20 and 21.

All patients then receive continuation therapy beginning on week 25 for arms I and II and week 33 for arms III and IV and continuing until week 130 for all arms.

Continuation

• Arms I and II: Patients receive oral 6-MP daily on weeks 25-130; oral DM twice a day on days 1-7 and VCR IV on days 1 and 8 during weeks 25, 41, 57, 73, 89, and 105; oral MTX weekly on weeks 25-130 (except during weeks of IT MTX); and MTX IT on weeks 25, 37, 49, 61, 73, 85, 97, and 109.

• Arms III and IV: Patients receive oral 6-MP daily on weeks 33-130; oral DM twice a day on days 1-7 and VCR IV on days 1 and 8 during weeks 41, 57, 73, 89, and 105; oral MTX weekly on weeks 33-130 (except during weeks of IT MTX); and MTX IT on weeks 37, 49, 61, 73, 85, 97, and 109.

Patients are followed every 2 months for 2 years, every 3 months for 1 year, every 6 months for 2 years, and then annually thereafter.

Xu H, Cheng C, Devidas M, et al.: ARID5B Genetic Polymorphisms Contribute to Racial Disparities in the Incidence and Treatment Outcome of Childhood Acute Lymphoblastic Leukemia. J Clin Oncol : , 2012.[PUBMED Abstract]

Rabin KR, Gramatges MM, Borowitz MJ, et al.: Absolute lymphocyte counts refine minimal residual disease-based risk stratification in childhood acute lymphoblastic leukemia. Pediatr Blood Cancer : , 2011.[PUBMED Abstract]

Borowitz MJ, Devidas M, Hunger SP, et al.: Prognostic signficance of end consolidation minimal residual disease (MRD) in childhood acute lymphoblastic leukemia (ALL): A report from the Children's Oncology Group (COG). [Abstract] J Clin Oncol 26 (Suppl 15): A-10000, 2008.

Borowitz MJ, Devidas M, Hunger SP, et al.: Clinical significance of minimal residual disease in childhood acute lymphoblastic leukemia and its relationship to other prognostic factors: a Children's Oncology Group study. Blood 111 (12): 5477-85, 2008.[PUBMED Abstract]

Davies SM, Borowitz MJ, Rosner GL, et al.: Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood 111 (6): 2984-90, 2008.[PUBMED Abstract]

Hinds PS, Hockenberry MJ, Gattuso JS, et al.: Dexamethasone alters sleep and fatigue in pediatric patients with acute lymphoblastic leukemia. Cancer 110 (10): 2321-30, 2007.[PUBMED Abstract]

Winick N, Martin PL, Devidas M, et al.: Delayed intensification (DI) enhances event-free survival (EFS) of children with B-precursor acute lymphoblastic leukemia (ALL) who received intensification therapy with six courses of intravenous methotrexate (MTX): POG 9904/9905: a Children's Oncology Group study (COG). [Abstract] Blood 110 (11): A-583, 2007.

Trial Contact Information

Trial Lead Organizations

Children's Oncology Group

Paul L. Martin, MD, Protocol chair		Ph: 919-668-1124

Registry Information
Official Title		ALINC #17 Treatment for Patients with Low Risk Acute Lymphoblastic Leukemia: A Pediatric Oncology Group Phase III Study
Trial Start Date		2000-04-07
Trial Completion Date		2007-07-15
Registered in ClinicalTrials.gov		NCT00005585
Date Submitted to PDQ		2000-02-11
Information Last Verified		2010-11-16
NCI Grant/Contract Number		CA30969

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