Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00005596
First received: May 2, 2000
Last updated: May 9, 2013
Last verified: May 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining more than one drug may kill more cancer cells. It is not yet known which regimen of chemotherapy is more effective for acute lymphoblastic leukemia.

PURPOSE: This randomized phase III trial is comparing four regimens of combination chemotherapy to see how well they work in treating children with newly diagnosed acute lymphoblastic leukemia.


Condition Intervention Phase
Leukemia
Drug: cyclophosphamide
Drug: cytarabine
Drug: daunorubicin hydrochloride
Drug: dexamethasone
Drug: leucovorin calcium
Drug: mercaptopurine
Drug: methotrexate
Drug: pegaspargase
Drug: thioguanine
Drug: vincristine sulfate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: ALinC 17: Protocol for Patients With Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL): A Phase III Study

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Improvement in outcome in children receiving multidrug delayed-intensification therapy [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
    The overall plan is to accrue for 3.1 years or until all accrual goals have been met, whichever occurs first. Since power is determined by event-rates, lower or higher than expected event rates could lead to an amendment to alter the accrual goal. This consideration will be made independent of arm-specific outcome, in order to eliminate bias


Secondary Outcome Measures:
  • Event-free survival, minimal residual disease, and early response [ Time Frame: 5 years ] [ Designated as safety issue: No ]
    The test statistic will compare Kaplan-Meier curves. Cox multiple regression will be utilized.

  • Occurrence of anticipated failures [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    An O'Brien-Fleming analysis will be conducted.

  • Total grade 3+ central nervous system (CNS) toxicity rates based on the National Cancer Institute Common Toxicity Criteria (NCI CTC) v2.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]

Enrollment: 1076
Study Start Date: April 2000
Primary Completion Date: July 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I
Patients receive IT methotrexate on day 1 followed by methotrexate IV over 20 minutes followed by methotrexate continuously over 23.6 hrs on wks 7, 10, 13, 16,19, and 22. At 42 hrs after the beginning of the methotrexate infusion, patients receive oral leucovorin calcium every 6 hrs for a total of 3 doses. Patients also receive oral mercaptopurine daily beginning on wk 5 and continuing until the completion of consolidation therapy; oral dexamethasone twice daily on days 1-7 of wks 8 and 17; and vincristine sulfate IV on day 1 of wks 8, 9, 17, and 18.
Drug: dexamethasone
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.
Other Name: DEX
Drug: leucovorin calcium
5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX.
Drug: mercaptopurine
50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC > 500/μL and platelets > 75,000/uL
Other Name: 6-MP
Drug: methotrexate

IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22.

IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22.

Other Name: MTX
Drug: vincristine sulfate
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)
Other Name: VCR
Experimental: Arm II
Patients receive methotrexate IV over 4 hours on weeks 7, 10, 13, 16, 19, and 22. At 42 hours after the beginning of the methotrexate infusion, patients receive oral leucovorin calcium as in arm I. Patients also receive mercaptopurine, dexamethasone, vincristine sulfate, and IT methotrexate as in arm I.
Drug: dexamethasone
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.
Other Name: DEX
Drug: leucovorin calcium
5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX.
Drug: mercaptopurine
50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC > 500/μL and platelets > 75,000/uL
Other Name: 6-MP
Drug: methotrexate

IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22.

IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22.

Other Name: MTX
Drug: vincristine sulfate
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)
Other Name: VCR
Experimental: Arm III
Patients receive methotrexate 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 wk 16; oral mercaptopurine daily on wks 5-13, and from wk 24 until the completion of consolidation therapy. Patients also receive IT methotrexate as in arm I on wks 7, 10, 13, 16, 20, 21, and 30; oral dexamethasone 2x daily on weeks 8, 16-18, and 28 for a total of 35 days; vincristine sulfate IV on day 1 of wks 8, 9, 16, 17, 18, 28, and 29; daunorubicin hydrochloride IV on day 1 of wks 16-18; cyclophosphamide IV over 30 minutes on day 1 of week 20; cytarabine IV or subcutaneously daily on days 2-5 of wks 20 and 21; and oral thioguanine daily on wks 20-21.
Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride
30 mg/m2 IV Day 1 of weeks 16, 17, and 18. Give Week 16 dose if ANC ≥ 500/μL and platelets ≥ 75,000/μL. Continue to give during Weeks 17 and 18, even in the face of uncomplicated myelosuppression
Other Name: daunomycin
Drug: dexamethasone
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.
Other Name: DEX
Drug: leucovorin calcium
5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX.
Drug: mercaptopurine
50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC > 500/μL and platelets > 75,000/uL
Other Name: 6-MP
Drug: methotrexate

IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22.

IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22.

Other Name: MTX
Drug: pegaspargase
2,500 IU/m2 will be given IM x 1 on Days 2,3,or 4 of Week 16; > or = 1 day after the IT MTX
Other Name: PEG
Drug: thioguanine
60 mg/m2 po qhs during Weeks 20 and 21 (total 14 days). Start week 20 when ANC > or = 500/ul and platelets > or = 75,000/uL. Continue to give all 14 doses despite uncomplicated myelosuppression.
Other Name: 6-TG
Drug: vincristine sulfate
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)
Other Name: VCR
Experimental: Arm IV
Patients receive methotrexate IV as in arm II on weeks 7, 10, 13, 24, 27, and 30; leucovorin calcium as in arm I; and pegaspargase, mercaptopurine, IT methotrexate, dexamethasone, vincristine sulfate, daunorubicin hydrochloride, cyclophosphamide, cytarabine, and thioguanine as in arm III.
Drug: cyclophosphamide Drug: cytarabine Drug: daunorubicin hydrochloride
30 mg/m2 IV Day 1 of weeks 16, 17, and 18. Give Week 16 dose if ANC ≥ 500/μL and platelets ≥ 75,000/μL. Continue to give during Weeks 17 and 18, even in the face of uncomplicated myelosuppression
Other Name: daunomycin
Drug: dexamethasone
6 mg/m2/day divided BID for 7 days during weeks 8 and 17.
Other Name: DEX
Drug: leucovorin calcium
5 mg/m2/dose of leucovorin will be given PO q12h x 2 doses beginning 48 hours after the start of the MTX.
Drug: mercaptopurine
50 mg/m2 dose po qhs Weeks 5 through 13 (total 9 wks) and from Week 24 until the end of consolidation. Only hold for uncomplicated myelosuppression, only if IV MTX course is delayed, until ANC > 500/μL and platelets > 75,000/uL
Other Name: 6-MP
Drug: methotrexate

IV: 1 gm/m2 given as a 200 mg/m2 bolus over 20 min followed by 800 mg/m2 over 23.6 hours given during Weeks 7, 10, 13, 16, 19, and 22.

IT: Doses by age, Weeks 7, 10, 13, 16, 19 and 22.

Other Name: MTX
Drug: pegaspargase
2,500 IU/m2 will be given IM x 1 on Days 2,3,or 4 of Week 16; > or = 1 day after the IT MTX
Other Name: PEG
Drug: thioguanine
60 mg/m2 po qhs during Weeks 20 and 21 (total 14 days). Start week 20 when ANC > or = 500/ul and platelets > or = 75,000/uL. Continue to give all 14 doses despite uncomplicated myelosuppression.
Other Name: 6-TG
Drug: vincristine sulfate
1.5 mg/m2 IV on Day 1 of Weeks 8, 9, 17 and 18 (max 2 mg)
Other Name: VCR

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   1 Year to 21 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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

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

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • Not specified

Chemotherapy

  • Not specified

Endocrine therapy

  • Not specified

Radiotherapy

  • Not specified

Surgery

  • Not specified
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00005596

  Show 123 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Study Chair: Naomi J. Winick, MD Simmons Cancer Center
  More Information

Additional Information:
Publications:
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.
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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00005596     History of Changes
Other Study ID Numbers: 9905, COG-P9905, POG-9905, CDR0000067704, NCI-2012-02325
Study First Received: May 2, 2000
Last Updated: May 9, 2013
Health Authority: United States: Federal Government

Keywords provided by Children's Oncology Group:
untreated childhood acute lymphoblastic leukemia

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
6-Mercaptopurine
BB 1101
Cyclophosphamide
Cytarabine
Daunorubicin
Dexamethasone
Dexamethasone 21-phosphate
Dexamethasone acetate
Leucovorin
Levoleucovorin
Methotrexate
Pegaspargase
Thioguanine
Vincristine
Abortifacient Agents
Abortifacient Agents, Nonsteroidal
Alkylating Agents
Anti-Infective Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antidotes

ClinicalTrials.gov processed this record on October 29, 2014