Pegaspargase and Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia (Closed to Accrual 4-22-2011)

PRIMARY OBJECTIVES: I. To demonstrate that biweekly intravenous (IV) pegaspargase beginning with Consolidation and ending with completion of delayed intensification (DI) in combination with hemi-augmented BFM therapy (hABFM) is feasible and safe in children with high risk (HR) acute lymphoblastic leukemia (ALL). OUTLINE: Patients are stratified according to risk assignment (high-risk \[HR\]-average \[day 29 minimal residual disease (MRD) \< 0.01%\] vs HR-high \[MRD \>= 0.01%, presence of central nervous system \[CNS\]3 leukemia, testicular disease, myeloid/mixed lineage leukemia \[MLL\] rearrangement, hypodiploidy, or steroid therapy within the past month\]). Patients are assigned to 1 of 2 treatment groups.\* (Note: \*Amendment 2 \[4-22-2011\] requires changes in the regimens. See the changes below, after Maintenance therapy.) INDUCTION THERAPY: All patients receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; prednisone IV or orally (PO) twice daily (BID) on days 1-28; daunorubicin hydrochloride IV over 15 minutes on days 1, 8, 15, and 22; methotrexate IT on days 8 and 29\*; and pegaspargase IV over 1-2 hours on day 4. (Note: \*Patients with CNS3 disease \[white blood cells \[(WBC)\] \>= 5/uL and positive for blasts on cytospin\] also receive methotrexate IT on days 15 and 22.) CONSOLIDATION THERAPY (begins on day 36 of induction therapy): GROUP A (HR-AVERAGE): Patients receive cyclophosphamide IV over 1 hour on days 1 and 29; cytarabine IV over 15 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD) on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43, and 50; methotrexate IT on days 1, 8, 15\*, and 22\*; and pegaspargase IV over 1-2 hours on days 15 and 43. GROUP B (HR-HIGH): Patients receive cyclophosphamide, cytarabine, mercaptopurine, vincristine sulfate, and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks. Patients with CNS3 disease undergo cranial radiotherapy QD for 10 days and patients with testicular disease undergo testicular radiotherapy QD for 12 days, beginning on day 1 of consolidation. (Note: \*Patients with CNS3 disease \[WBC \>= 5/uL and positive for blasts on cytospin\] do not receive methotrexate IT on days 15 and 22.) Interim maintenance (IM) therapy (begins on day 57 of consolidation): GROUP A: Patients receive vincristine sulfate IV on days 1, 11, 21, 31, and 41; methotrexate IV over 10-15 minutes on days 1, 11, 21, 31, and 41; methotrexate IT on days 1 and 31; and pegaspargase IV over 1-2 hours on days 2 and 22. GROUP B: Patients receive vincristine sulfate and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks. DI therapy (begins on day 57 of IM): GROUP A: Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 15 minutes on days 1, 8, and 15; cyclophosphamide IV over 1 hour on day 29; cytarabine IV over 15 minutes or SC on days 29-32 and 36-39; thioguanine PO on days 29-42; methotrexate IT on days 1, 29, and 36; and pegaspargase IV over 1-2 hours on days 4 and 43. GROUP B: Patients receive vincristine sulfate, dexamethasone, doxorubicin hydrochloride, cyclophosphamide, cytarabine, thioguanine, and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks. MAINTENANCE THERAPY (MT; begins on day 57 of DI): All patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84; methotrexate IT on day 1; and methotrexate PO BID on days 8, 15, 22, 29\*, 36, 43, 50, 57, 64, 71, and 78. In both groups, MT repeats every 12 weeks until total duration of therapy is 2 years from the start of IM for female patients and 3 years from the start of IM for male patients. Patients in Group B who did not undergo radiotherapy to the brain during consolidation therapy undergo prophylactic cranial radiotherapy (CR) daily for 8 days. (\[Note: \*Patients in Group A also receive methotrexate IT on day 29 of courses 1-4 \[no oral methotrexate\]). REVISED MT (RMT): The regimen is the same as standard MT, but 2 of the doses of IT methotrexate are omitted (day 29 of courses 3 and 4).