Multicentric Study for the Treatment of Children With Acute Lymphoblastic Leukemia

Brief Summary

Detailed Description

OBJECTIVES: * Determine the dose of daunorubicin hydrochloride that is equivalent to 30 mg/m² of doxorubicin hydrochloride in pediatric patients with acute lymphoblastic leukemia (ALL). * Determine whether it is possible to reduce therapy in pediatric patients with low-risk ALL and a PVA (prednisolone-vincristine-asparaginase) score of 3+4 without loss of efficacy. * Investigate the role of single nucleotide polymorphisms of infection defense gene for infectious complications during therapy in these patients. * Reduce neurological complications by reducing doses of intrathecal methotrexate. * Reduce allergic reactions against asparaginase (ASP) by using pegaspargase after E. coli ASP. OUTLINE: This is a randomized, multicenter study. * Prephase: Patients are randomized to 1 of 3 treatment arms. * Arm I: Patients receive doxorubicin hydrochloride IV once. * Arm II: Patients receive daunorubicin hydrochloride IV once. * Arm III: Patients receive daunorubicin hydrochloride IV once at a higher dose than in arm II. * Induction phase: All patients receive vincristine IV 4 times weekly, daunorubicin hydrochloride IV 3 times weekly, and oral prednisolone daily for 4 weeks. * Intensive phase: Patients are stratified according to risk (low vs high). * Low-risk disease\*: Patients receive 4 courses of methotrexate IV and asparaginase intramuscularly (IM). * High-risk disease\*: Patients receive 6 courses of cyclophosphamide IV, methotrexate IV, and asparaginase IM. All patients also receive methotrexate IV, teniposide IV, cytarabine IV, high-dose cytarabine IV, and asparaginase IM after completion of the above regimen. * CNS phase: All patients receive intrathecal (IT) methotrexate for 3 doses and oral mercaptopurine for 4 weeks. Patients with T-cell acute lymphoblastic leukemia or patients who have blasts in cerebrospinal fluid at diagnosis or whose WBC \> 200/nL at diagnosis OR whose WBC between 100-200/nL at diagnosis and blasts \> 1/nL after prephase chemotherapy undergo cranial irradiation. * Reinduction phase: Patients are stratified according to risk (low vs high) * Low-risk disease\*: Patients receive 2 courses of doxorubicin hydrochloride IV, vincristine IV, and oral dexamethasone; pegaspargase IM once; and 1 course of cyclophosphamide IV, cytarabine IV, and oral thioguanine. * High-risk disease\*: Patients receive 4 courses of doxorubicin hydrochloride IV, vincristine IV, and oral dexamethasone; pegaspargase IM twice; and 2 courses of cyclophosphamide IV, cytarabine IV, and oral thioguanine. * Maintenance phase: All patients receive oral mercaptopurine daily and methotrexate IV once weekly for up to 2 years after diagnosis. NOTE: \*In addition to those defined in Disease Characteristics, patients who do not achieve remission after induction phase are treated as high-risk disease, patients who achieve remission after induction phase are treated as low-risk disease PROJECTED ACCRUAL: A total of 550 patients will be accrued for this study.

Primary Outcomes