OBJECTIVES: I. Improve the outcome of children with high-risk acute lymphoblastic leukemia treated with 2 different chemotherapy regimens. II. Determine the relative safety and efficacy of dexamethasone given for 14 days vs prednisone given for 28 days during induction. III. Determine the relative safety and efficacy of high-dose methotrexate (5gm/m\^2) with leucovorin rescue compared to escalating methotrexate without leucovorin rescue (Capizzi I) during interim maintenance I. IV. Correlate Day 29 minimal residual disease (MRD) with event-free survival (EFS) and overall survival (OS). V. Correlate early marrow response status with day-29 MRD status. VI. Improve outcome by identifying additional high risk patients by Day 29 MRD for treatment with fully augmented Berlin-Frankfurt-Munster (BFM). OUTLINE: This is a randomized, multicenter study. Patients are stratified according to early response (slow early response \[SER\] vs rapid early response \[RER\]). Induction therapy: Patients are randomized to 1 of 4 treatment arms. ARM I: Patients receive cytarabine intrathecally (IT) on day 1, vincristine intravenously (IV) and daunorubicin IV on days 1, 8, 15, and 22, dexamethasone orally (PO) or IV twice daily (BID) on days 1-14, methotrexate (MTX) IT on days 8 and 29\* and pegaspargase intramuscularly (IM) once on day 4, 5, or 6. NOTE: \*Patients with CNS3 disease (WBC > 5/mL in cerebrospinal fluid and positive for blasts on cytospin) also receive MTX IT on days 15 and 22. ARM II: Patients receive induction therapy as in Arm I. ARM III: Patients receive cytarabine, vincristine, daunorubicin, and pegaspargase as in Arm I. Patients also receive prednisone PO or IV BID on days 1-28 and MTX IT on days 8 and 29. ARM IV: Patients receive induction therapy as in Arm III. Patients in all arms are evaluated at day 29 of induction therapy. Patients with M3 disease are removed from study. Patients with M1 disease and less than 1% minimal residual disease (MRD) proceed to consolidation therapy beginning on day 36. Patients with M2 disease OR with MI disease and at least 1% MRD receive extended induction therapy for 2 additional weeks. Patients with SER disease and MLL rearrangements are removed from the study but may be eligible for treatment on protocol COG-AALL0031. Extended induction therapy: Patients continue to receive therapy on the arm to which they were originally randomized. ARMS I and II: Patients receive dexamethasone PO or IV BID on days 1-14, vincristine IV on days 1 and 8, daunorubicin IV on day 1 and pegaspargase IM on day 4, 5, or 6 and are then reevaluated. ARMS III and IV: Patients receive prednisone PO or IV BID on days 1-14, and vincristine, daunorubicin, and pegaspargase as in Arms I and II and are then reevaluated. Patients on all arms who have M1 disease and less than 1% MRD after extended induction proceed to consolidation therapy and continue as SER patients. All other patients are removed from study. Consolidation therapy: All patients receive cyclophosphamide IV over 30 minutes on days 1 and 29, cytarabine IV or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39, mercaptopurine (MP) PO on days 1-14 and 29-42, vincristine IV on days 15, 22, 43, and 50; pegaspargase IM on days 15 and 43 and MTX\* IT on days 1, 8, 15, and 22. Patients with testicular disease also receive radiotherapy to the testes. NOTE: \*Patients with CNS3 disease receive MTX on days 1 and 8 only. Interim maintenance therapy I: Patients continue to receive treatment on the arm to which they were originally randomized. ARM I: (escalating-dose MTX) Patients receive vincristine IV and escalating-dose MTX IV on days 1, 11, 21, 31, and 41, pegaspargase IM on days 2 and 22 and MTX IT on days 1 and 21. ARM II: (high-dose MTX) Patients receive vincristine IV and high-dose methotrexate IV over 24 hours on days 1, 15, 29, and 43, MP PO on days 1-56 and IT MTX on days 1 and 29. Patients also receive leucovorin calcium IV every 6 hours for at least 3 doses, beginning 42 hours after start of each MTX infusion. ARM III: (escalating-dose MTX) Patients receive interim maintenance I therapy as in Arm I. ARM IV: (high-dose MTX) Patients receive interim maintenance I therapy as in Arm II. DELAYED INTENSIFICATION THERAPY I: All patients receive vincristine IV on days 1, 8, 15, 43, and 50, dexamethasone PO or IV BID on days 1 to 21 for patients age 1 to 12 OR on days 1-7 and 15-21 for patients age 13 and over, doxorubicin IV on days 1, 8, and 15, pegaspargase IM on day 4, 5, or 6 AND day 43, cyclophosphamide IV over 30 minutes on day 29, cytarabine IV or SC on days 30-33 and 37-40, thioguanine PO on days 29-42 and MTX IT on days 1, 29, and 36.After delayed intensification I, SER patients proceed to interim maintenance II and delayed intensification II. RER patients proceed directly to maintenance. INTERIM MAINTENANCE THERAPY II: All patients receive vincristine IV and MTX IV on days 1, 11, 21, 31, and 41, pegaspargase IM on days 2 and 22; and MTX IT on days 1 and 21. Patients then proceed to delayed intensification II. DELAYED INTENSIFICATION THERAPY II: All patients receive therapy as in delayed intensification I, arm I. CNS3 patients also receive radiotherapy for 3-10 days, beginning on day 29. All other SER patients, patients with MLL rearrangements, and some patients pretreated with steroids (> 48 hours within the week prior to diagnosis) receive prophylactic cranial radiotherapy (CRT) for 8 days, beginning on day 29. Patients then proceed to maintenance therapy. MAINTENANCE THERAPY: All patients receive vincristine IV on days 1, 29, and 57, dexamethasone PO BID on days 1-5, 29-33, and 57-61, MP PO on days 1-84, MTX IT on day 1\*; and MTX PO on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78. NOTE: \*RER (who did not undergo CRT) patients also receive MTX IT on day 29 for maintenance courses 1-4. In all arms, maintenance therapy repeats every 12 weeks until total duration of therapy is 2 years from the start of interim maintenance I for female patients and 3 years from the start of interim maintenance I for male patients. Patients with testicular disease may receive testicular radiotherapy for 8 days during one of the first 3 courses of maintenance therapy. 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 annually thereafter.
Inclusion Criteria: * Must be eligible for and enrolled on classification study COG-AALL03B1 * Newly diagnosed B-precursor acute lymphoblastic leukemia * WBC \> 50,000/mm\^3 for patients age 1 to 9 * Any WBC for patients age 10 to 30 OR patients who have received prior steroid therapy OR patients with testicular disease * Whit blood cell (WBC) criteria: * Age 1 - 9 years: WBC \>= 50,000/uL * Age 10 - 30 years: any WBC * Prior steroid therapy: any WBC * Testicular disease: any WBC * Patients shall have had no other prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine * Patients receiving prior steroid therapy (as described in AALL03B1) are eligible for study; the dose and duration of previous steroid therapy should be carefully documented * All patients and/or their parents or legal guardians must sign a written informed consent * All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met Exclusion Criteria: * Patients with Down syndrome are ineligible to enroll onto this study
are designated in this study