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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

May 2, 2000
May 9, 2013
April 2000
July 2005   (final data collection date for primary outcome measure)
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
Not Provided
Complete list of historical versions of study NCT00005596 on ClinicalTrials.gov Archive Site
  • 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 ]
Not Provided
Not Provided
Not Provided
 
Combination Chemotherapy in Treating Children With Newly Diagnosed Acute Lymphoblastic Leukemia
ALinC 17: Protocol for Patients With Newly Diagnosed Standard Risk Acute Lymphoblastic Leukemia (ALL): A Phase III Study

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.

OBJECTIVES:

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

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.

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

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Leukemia
  • 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 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.
    Interventions:
    • Drug: dexamethasone
    • Drug: leucovorin calcium
    • Drug: mercaptopurine
    • Drug: methotrexate
    • Drug: vincristine sulfate
  • 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.
    Interventions:
    • Drug: dexamethasone
    • Drug: leucovorin calcium
    • Drug: mercaptopurine
    • Drug: methotrexate
    • Drug: vincristine sulfate
  • 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.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: cytarabine
    • Drug: daunorubicin hydrochloride
    • Drug: dexamethasone
    • Drug: leucovorin calcium
    • Drug: mercaptopurine
    • Drug: methotrexate
    • Drug: pegaspargase
    • Drug: thioguanine
    • Drug: vincristine sulfate
  • 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.
    Interventions:
    • Drug: cyclophosphamide
    • Drug: cytarabine
    • Drug: daunorubicin hydrochloride
    • Drug: dexamethasone
    • Drug: leucovorin calcium
    • Drug: mercaptopurine
    • Drug: methotrexate
    • Drug: pegaspargase
    • Drug: thioguanine
    • Drug: vincristine sulfate

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
1076
Not Provided
July 2005   (final data collection date for primary outcome measure)

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
Both
1 Year to 21 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Australia,   Canada,   Netherlands,   Puerto Rico,   Switzerland
 
NCT00005596
9905, COG-P9905, POG-9905, CDR0000067704, NCI-2012-02325
Yes
Children's Oncology Group
Children's Oncology Group
National Cancer Institute (NCI)
Study Chair: Naomi J. Winick, MD Simmons Cancer Center
Children's Oncology Group
May 2013

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