Combination Chemotherapy in Treating Children With Acute Lymphoblastic Leukemia
Condition: Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Study type: Interventional
Phase: Phase 3

Summary: 
      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 combination chemotherapy is more effective for childhood acute
      lymphoblastic leukemia.

      PURPOSE: This randomized phase III trial is comparing different regimens of combination
      chemotherapy to see how well they work in treating children with acute lymphoblastic
      leukemia.
    

Detailed description: 
      OBJECTIVES:

        -  Compare the efficacy and toxicity of short methotrexate infusion vs longer infusion in
           patients with low-risk acute lymphoblastic leukemia.

        -  Compare the efficacy of these regimens of methotrexate, with or without multidrug
           intensification, in these patients.

      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.

      PROJECTED ACCRUAL: A total 902 patients will be accrued for this study within 3.22 years.
    

Intervention name(s): cyclophosphamide; cytarabine; daunorubicin hydrochloride; dexamethasone; leucovorin calcium; mercaptopurine; methotrexate; pegaspargase; thioguanine; vincristine sulfate
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Given IV; Deoxycytidine analogue which is metabolized to ARA-CTP, a substance which inhibits DNA polymerase.; Given IV; Dexamethasone is a synthetic fluorinated glucocorticoid devoid of mineralocorticoid effects.; Synthetic d,l-5 CHO tetrahydrofolate, which is used to bypass the inhibition of dihydrofolate reductase by Methotrexate (MTX); An analogue of the nucleic acid constituent adenine and the physiological purine base hypoxanthine; A folate analogue which inhibits the enzyme dihydrofolate reductase, haltin g DNA, RNA, and protein synthesis; E-Coli asparaginase deaminates asparagine, thus, is lethal for cells which cannot synthesize asparagine.; Given orally; Given IV
Other intervention name(s): Cytoxan; NSC #26271; cytosine arabinoside; Ara-C; Cytosar; NSC #063878; Daunomycin; rubidomycin; Cerubidine; NSC #82151; Decadron; NSC#034521; LCV; Wellcovorin; citrovorum factor; folinic acid; NSC#003590; 6-MP; Purinethol; NSC #00075; MTX; amethopterin; NSC#00740; IND#4291; E Coli; Elspar; asparaginase; Erwinia; PEG; NSC#109229; 6-thioguanine; 2-amino-1; 7-dihydro-6H-purine-6-thione; WR-1141; Tabloid; Lanvis; NSC # 752; Oncovin; VCR; LCR; NSC #67574
Intervention MeSH terms: Leucovorin; Cytarabine; Dexamethasone; Cyclophosphamide; Methotrexate; Vincristine; Daunorubicin; Asparaginase; Mercaptopurine; Pegaspargase; Thioguanine; Levoleucovorin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: childhood acute lymphoblastic leukemia in remission; B-cell childhood acute lymphoblastic leukemia