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

Alternate Title

Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia

Basic Trial Information

Objectives

1. Determine if multidrug delayed-intensification therapy improves outcome in children with newly diagnosed standard-risk acute lymphocytic leukemia.
2. Compare the efficacy and toxicity of methotrexate administered over 4 hours vs methotrexate administered over 24 hours in this patient population.
3. Determine the correlation between event-free survival, minimal residual disease, and early response in this patient population treated with this multiple drug regimen.

Entry Criteria

Disease Characteristics:

• Confirmed diagnosis of newly diagnosed B-precursor acute lymphocytic leukemia

• Standard risk (not low, high, or very high risk)

• Prior registration and treatment on POG 9900 Classification Study

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 21 at diagnosis

Performance status:

• Not specified

Life expectancy:

• Not specified

Hematopoietic:

• Not specified

Hepatic:

• Not specified

Renal:

• Not specified

Other:

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

Expected Enrollment

A total of 1,014 patients will be accrued for this study within 3.22 years.

Outline

This is a randomized, multicenter study.

• Induction (weeks 1-4): Patients receive induction therapy on POG 9900.

• Consolidation (weeks 5-32): Patients are randomized to one of four treatment arms. Patients with t(1;19) are randomized to either arm III or arm IV.
  • Arm I (weeks 5-24): Patients receive IT methotrexate (MTX) on day 1 followed by MTX IV over 20 minutes followed by MTX continuously over 23.6 hours on weeks 7, 10, 13, 16,19, and 22. At 42 hours after the beginning of the MTX infusion, patients receive oral leucovorin calcium every 6 hours for a total of 3 doses. Patients also receive oral mercaptopurine daily beginning on week 5 and continuing until the completion of consolidation therapy; oral dexamethasone twice daily on days 1-7 of weeks 8 and 17; and vincristine IV on day 1 of weeks 8, 9, 17, and 18.

  • Arm II (weeks 5-24): Patients receive MTX IV over 4 hours on weeks 7, 10, 13, 16, 19, and 22. At 42 hours after the beginning of the MTX infusion, patients receive oral leucovorin calcium as in arm I. Patients also receive mercaptopurine, dexamethasone, vincristine, and IT MTX as in arm I.

  • Arm III (weeks 5-32): Patients receive MTX IV as in arm I on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; pegaspargase IM on day 2, 3, OR 4 of week 16; and oral mercaptopurine daily on weeks 5-13, and from week 24 until the completion of consolidation therapy. Patients also receive IT MTX as in arm I on weeks 7, 10, 13, 16, 20, 21, and 30; oral dexamethasone twice daily on weeks 8, 16-18, and 28 for a total of 35 days; vincristine IV on day 1 of weeks 8, 9, 16, 17, 18, 28, and 29; daunorubicin IV on day 1 of weeks 16-18; cyclophosphamide IV over 30 minutes on day 1 of week 20; cytarabine IV or subcutaneously daily on days 2-5 of weeks 20 and 21; and oral thioguanine daily on weeks 20-21.

  • Arm IV (weeks 5-32): Patients receive MTX IV as in arm II on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; and pegaspargase, mercaptopurine, IT MTX, dexamethasone, vincristine, daunorubicin, cyclophosphamide, cytarabine, and thioguanine as in arm III.

• Intensive continuation (weeks 25-80): At weeks 25-72 for arms I and II, and at weeks 33-80 for arms III and IV, patients receive oral MTX every 6 hours for 4 doses on weeks 1, 3, 5, 7, 9, and 11; oral mercaptopurine daily; oral leucovorin calcium every 12 hours for 2 doses beginning 48 hours after the start of MTX; IT MTX and vincristine IV on day 1 of week 12; and oral dexamethasone twice daily on days 1-7, beginning with the administration of vincristine. Treatment repeats every 12 weeks for 4 courses.

• Additional continuation (weeks 73-130): At weeks 73-130 for arms I and II, and at weeks 81-130 for arms III and IV, patients receive oral MTX weekly; oral mercaptopurine daily; vincristine IV on day 1 every 12 weeks; oral dexamethasone as during intensive continuation therapy; and IT MTX on day 1 every 12 weeks, beginning with the last week of the first course (in place of oral MTX).

Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, every 6 months for 1 year, and then every 6-12 months for 1 year.

Chen I, Harvey R, Mullighan CG, et al.: Relationship of CRLF2 expression and outcome in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL): A report from the Children’s Oncology Group. [Abstract] J Clin Oncol 29 (Suppl 15): A-9505, 2011.

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

Naomi Winick, MD, Protocol chair		Ph: 214-648-3074; 866-460-4673 Email: naomi.winick@utsouthwestern.edu

Related Information

PDQ® clinical trial COG-ACCL01P3

Registry Information
Official Title		ALinC 17: Protocol for Patients with Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL): A Phase III Study
Trial Start Date		2000-04-07
Trial Completion Date		2007-07-15
Registered in ClinicalTrials.gov		NCT00005596
Date Submitted to PDQ		2000-02-29
Information Last Verified		2010-11-16
NCI Grant/Contract Number		CA30969

Back to Top