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About
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective in treating acute lymphoblastic leukemia.
PURPOSE: This randomized clinical trial is studying the side effects of two combination chemotherapy regimens and to see how well they work in treating children with newly diagnosed acute lymphoblastic leukemia.
Full description
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study. Patients are stratified according to risk (high vs intermediate vs standard), age in years (0 to 5 vs 6 to 9 vs 10 to 17), and sex.
Patients with standard-risk disease:
Induction therapy: Patients receive prednisolone IV or orally three times daily on days 1-7; oral dexamethasone three times daily on days 8-28; asparaginase IV over 1 hour or intramuscularly once on days 8, 11, 14, 17, 20, 23, 26, and 29; vincristine IV once on days 8, 15, 22, and 29; daunorubicin hydrochloride IV over 1 hour on days 8 and 15; and methotrexate intrathecally (IT) once on days 1, 15, and 33.
Early intensification (EI) therapy: Patients receive cyclophosphamide IV over 1 hour on day 36, cytarabine IV continuously on days 38-41 and 45-48, oral mercaptopurine once daily on days 36-50, and methotrexate IT on days 38 and 45.
Consolidation therapy: Two weeks after completing EI therapy, patients receive oral mercaptopurine once daily on days 1-56 and methotrexate IV over 24 hours and IT on days 8, 22, 36, and 50.
Delayed intensification (DI) therapy:
Maintenance therapy: Patients are randomized to one of two treatment arms. Patients who do not consent for randomization receive conventional therapy (arm I).
Patients with intermediate-risk disease:
Induction therapy: Patients receive prednisolone, dexamethasone, and asparaginase as in standard-risk induction therapy. Patients also receive vincristine IV and daunorubicin hydrochloride IV over 1 hour on days 8, 15, 22, and 29; methotrexate IT on day 1; and triple intrathecal therapy (TIT; high-dose methotrexate, cytarabine, hydrocortisone sodium succinate) on days 15 and 33.
First EI therapy: Patients receive cyclophosphamide, cytarabine, and mercaptopurine as in standard-risk EI. Patients also receive TIT on day 38.
Second EI therapy: Beginning 2 weeks after completing first EI, patients receive cyclophosphamide over 1 hour on day 1, oral mercaptopurine on days 1-14, cytarabine IV on days 3-6 and 10-13, and TIT on day 3.
Consolidation therapy: Beginning 2 weeks after completing second EI, patients receive mercaptopurine as in standard-risk consolidation therapy. Patients also receive methotrexate IV over 24 hours and TIT on days 8, 22, 36, and 50.
First DI therapy: Patients receive treatment as in standard-risk DI.
Interim maintenance therapy: Patients receive oral mercaptopurine and oral methotrexate on days 1-56.
Second DI therapy: Patients receive DI/a and D1/b (without methotrexate) as in standard-risk DI. Patients also receive TIT on days 31 and 38.
Maintenance therapy: Patients are randomized to 1 of 2 treatment arms:
Patients with high-risk disease:
Induction therapy: Patients receive treatment as in intermediate-risk induction therapy.
First EI therapy: Patients receive treatment as in intermediate-risk first EI.
Second EI therapy: Patients receive treatment as in intermediate-risk second EI.
Consolidation therapy (interval between blocks is 2 weeks):
Blocks 1-3 are then repeated once. Patients then proceed to delayed intensification therapy.
Delayed intensification therapy: Patients receive dexamethasone orally or IV three times daily on days 1-7 and 15-21; doxorubicin hydrochloride IV and vincristine IV on days 8, 15, 22, and 29; and asparaginase IV on days 8, 11, 15, and 18. Patients also receive cyclophosphamide IV on day 36, cytarabine IV on days 38-41 and 45-48, thioguanine IV on days 36-49, and TIT on days 38 and 45.
Maintenance therapy: Patients receive oral mercaptopurine and oral methotrexate once daily on days 1-14, cyclophosphamide over 1 hour and cytarabine over 1 hour once between days 15-21, oral dexamethasone two or three times daily for 5 days between days 29-35, vincristine IV on day 29, and TIT on day 22. Treatment repeats every 4 weeks. After 10 courses, patients no longer receive TIT. After 12 courses, patients no longer receive cyclophosphamide and cytarabine. At this time patients continue mercaptopurine and methotrexate on days 1-21. After 20 courses, patients no longer receive dexamethasone or vincristine. At this time, patients continue mercaptopurine and methotrexate on days 1-28. Females receive up to 17 courses and males up to 23 courses.
Some patients may also undergo radiotherapy or stem cell transplantation.
Enrollment
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Inclusion and exclusion criteria
DISEASE CHARACTERISTICS:
Newly diagnosed acute lymphoblastic leukemia meeting 1 of the following risk definitions:
Standard-risk disease:
Age 1 to 9 years
White blood cell (WBC) < 50/mm^3 OR t(12;21) or molecular fusion product -positive disease
Good response to prior prednisone (day 8 peripheral blood blast < 1,000/mm^3)
None of the following subtypes:
Bone marrow (BM) M1 or M2 on day 15, BM remission (< 5% blast) on day 33
Intermediate-risk disease:
Good response to prior prednisone
BM M1/M2 on day 15
Meets 1 of the following criteria:
High-risk disease, meeting 1 of the following criteria:
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
Primary purpose
Allocation
Interventional model
Masking
2,231 participants in 2 patient groups
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Data sourced from clinicaltrials.gov
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