Combination Chemotherapy in Treating Children With Anaplastic Large Cell Lymphoma (ALCL 99)

OBJECTIVES: * Compare the event-free survival in children with anaplastic large cell lymphoma treated with various induction and maintenance chemotherapy regimens with or without vinblastine. * Compare the impact of different doses and schedules of methotrexate from the Berlin-Frankfurt-Munster-K2 Protocol in terms of overall survival, complete remission rate, CNS relapse rate, and nonlymphoma-related death and early death rates in these patients. OUTLINE: This is a randomized, multicenter study. Patients are stratified according to country, vinblastine (VBL) (yes vs no), and prognostic factors (standard-risk (SR) vs high-risk (HR) disease). Beginning immediately after confirmation of diagnosis, patients receive prephase therapy comprising dexamethasone (DM) IV or orally daily on days 1 and 2 and every 12 hours on days 3-5; cyclophosphamide (CTX) IV over 1 hour on days 1 and 2; and methotrexate (MTX) intrathecally (IT), doxorubicin (DOX) IV, and hydrocortisone (HC) IT on day 1. Patients are then assigned to one of two treatment groups based on prognosis: * Group 1 (SR disease): Patients are randomized to arm I or III: * Arm I: Patients receive treatment on arm I as defined below on day 1, and then the following courses as defined below in the following order beginning on day 6: A1, B1, A2, B2, A3, and B3. * Arm III: Patients receive treatment on arm III as defined below on day 1, and then the following courses as defined below in the following order beginning on day 6: regimen AM1, BM1, AM2, BM2, AM3, and BM3. * Group 2 (HR disease): * First randomization: Patients are randomized to arm I or III: * Arm I: Patients receive treatment on arm I as defined below on day 1 and then course A1 as defined below on day 6. * Arm III: Patients receive treatment on arm III as defined below on day 1 and then course AM1 as defined below on day 6. * Second randomization: Patients without disease progression after completion of the above therapy are randomized to arm I, II, III, or IV. * Arm I: Patients receive treatment on arm I as defined below on day 1, and then the following courses as defined below in the following order after blood counts recover: B1, A2, B2, A3, and B3. * Arm II: Patients receive treatment on arm II as defined below on day 1, and then the following courses as defined below in the following order after blood counts recover: BV1, AV2, BV2, AV3, and BV3. * Arm III: Patients receive treatment on arm III as defined below on day 1, and then the following courses as defined below in the following order after blood counts recover: BM1, AM2, BM2, AM3, and BM3. * Arm IV: Patients receive treatment on arm IV as defined below on day 1, and then the following courses as defined below in the following order after blood counts recover: BMV1, AMV2, BMV2, AMV3, and BMV3. Patients are followed every 2 months for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually thereafter. DEFINITIONS: * Arms I-IV are defined below: * Arm I: Patients receive lower dose MTX IV over 24 hours and MTX IT. * Arm II: Patients receive lower dose MTX IV over 24 hours and MTX IT. Patients with HR disease also receive VBL IV weekly for 1 year beginning 3 weeks after initiation of course BV3. * Arm III: Patients receive higher dose MTX IV over 3 hours without intrathecal therapy. * Arm IV: Patients receive treatment as in arm III. Patients with HR disease also receive VBL IV weekly for 1 year beginning 3 weeks after initiation of course BMV3. * Regimens A, B, AV, BV, AM, BM, AMV, and BMV are defined below: * Regimen A (courses A1, A2, and A3): Patients receive DM IV or orally every 12 hours on days 1-5; MTX IV over 24 hours on day 1; MTX IT, DOX IV and HC IT (beginning 2-4 hours after initiation of MTX infusion) on day 1; leucovorin calcium (CF) IV rescue at 42, 48, and 54 hours after initiation of MTX infusion; ifosfamide (IFF) IV over 1 hour on days 1-5 (before initiation of MTX infusion); cytarabine (ARA-C) IV over 1 hour every 12 hours and etoposide (VP-16) IV over 2 hours once (beginning after completion of ARA-C infusion) on days 4 and 5. Each course lasts 3 weeks. * Regimen B (courses B1, B2, and B3): Patients receive DM, MTX, intrathecal therapy, and CF rescue as in regimen A. Patients also receive CTX IV over 1 hour on days 1-5 and DOX IV over 1 hour on days 4 and 5. Each course lasts 3 weeks. * Regimen AV (courses AV1, AV2, and AV3): Patients receive treatment as in regimen A and VBL IV on day 1. Each course lasts 3 weeks. * Regimen BV (courses BV1, BV2, and BV3): Patients receive treatment as in regimen B and VBL IV as in regimen AV. Each course lasts 3 weeks. * Regimen AM (courses AM1, AM2, and AM3): Patients receive DM IV or orally every 12 hours on days 1-5; MTX IV over 3 hours on day 1; and CF IV rescue every 6 hours for a total of 12 doses beginning 24 hours after initiation of MTX infusion. Patients also receive IFF, ARA-C, and VP-16 as in regimen A. Each course lasts 3 weeks. * Regimen BM (courses BM1, BM2, and BM3): Patients receive CTX and DOX as in regimen B. Patients also receive DM, MTX, and CF rescue as in regimen AM. Each course lasts 3 weeks. * Regimen AMV (courses AMV1, AMV2, and AMV3): Patients receive treatment as in regimen AM and VBL as in regimen AV. Each course lasts 3 weeks. * Regimen BMV (courses BMV1, BMV2, and BMV3): Patients receive treatment as in regimen BM and VBL as in regimen AV. Each course lasts 3 weeks. PROJECTED ACCRUAL: A total of 400 patients will be accrued for this study within 5.4-6.7 years.