Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia

PRIMARY OBJECTIVES: I. To test whether the relapse-free survival after allogeneic stem cell transplantation among Philadelphia chromosome positive and/or breakpoint cluster region (BCR)/Abelson murine leukemia viral oncogene (ABL) positive acute lymphoblastic leukemia (ALL) patients given an intensive short-term chemotherapy regimen of fractionated cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (hyper-CVAD) in combination with the tyrosine kinase inhibitor dasatinib is sufficiently high to warrant further investigation. SECONDARY OBJECTIVES: I. To test whether the continuous complete remission rate for previously untreated Philadelphia chromosome positive and/or BCR/ABL positive acute lymphoblastic leukemia (ALL) patients given an intensive short-term chemotherapy regimen of hyper-CVAD in combination with the tyrosine kinase inhibitor dasatinib is sufficiently high to warrant phase III investigation. II. To investigate in a preliminary manner the relative effectiveness of minimal residual disease (MRD) detection using real-time quantitative polymerase chain reaction (PCR) for BCR/ABL versus flow cytometry to predict the outcome of patients treated by the hyper-CVAD + dasatinib regimen and/or allogeneic stem cell transplant. TERTIARY OBJECTIVES: I. To estimate the frequency and severity of toxicities of the intensive short-term chemotherapy regimen in these patients. II. To estimate the overall survival of all patients on this study. OUTLINE: INDUCTION/CONSOLIDATION THERAPY: All patients receive both of the following regimens in alternating courses: COURSES 1, 3, 5, 7 or 3, 5, 7, 9: Patients receive cyclophosphamide intravenously (IV) over 3 hours twice daily (BID) on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 30 minutes on days 4 and 11; dexamethasone IV or orally (PO) once daily (QD) on days 1-4 and 11-14; dasatinib PO QD on days 1-14; cytarabine intrathecally (IT) on day 7; methotrexate IT on day 2; and filgrastim (G-CSF) subcutaneously (SC) QD or BID. COURSES 2, 4, 6, 8: Patients receive high-dose methotrexate IV over 24 hours on day 1; methylprednisolone IV over 30 minutes BID on days 1-3; dasatinib PO QD on days 1-14; high-dose cytarabine IV over 2 hours BID on days 2-3; leucovorin calcium IV on days 2 or 3; methotrexate IT on day 2; cytarabine IT on day 7; and G-CSF SC QD or BID. Treatment repeats every 14-21 days for 8 courses in the absence of disease progression, unacceptable toxicity, or if patient achieves complete remission (CR) or complete remission with incomplete platelet recovery (CRi). MAINTENANCE THERAPY\*: Patients receive vincristine sulfate IV over 30 minutes on day 1, prednisone PO QD on days 1-5, and dasatinib PO QD on days 1-28. Treatment repeats every month for 24 courses in the absence of disease progression or unacceptable toxicity or until the transplant is ready. INTENSIFICATION: For courses 6 and 13, patients receive cyclophosphamide IV over 3 hours BID on days 1-3; doxorubicin hydrochloride IV over 24 hours on day 4; vincristine sulfate IV over 30 minutes on days 4 and 11; dexamethasone IV or PO QD on days 1-4 and 11-14; dasatinib PO QD on days 1-14; and G-CSF SC QD or BID. NOTE: \*Only if transplantation is not ready after induction/consolidation therapy or patients are not undergoing a transplant. ALLOGENEIC STEM CELL TRANSPLANTATION (FOR PATIENTS ACHIEVING CR OR CRi): CONDITIONING REGIMEN: Patients receive 1 of the following regimens: REGIMEN A: Patients receive total-body irradiation (TBI) QD on days -7 to -4 and cyclophosphamide IV on days -3 and -2. REGIMEN B: Patients receive TBI BID on days -6 to -4 and cyclophosphamide IV on days -3 and -2. REGIMEN C: Patients receive cyclophosphamide IV on days -7 and -6 and TBI QD on days -4 to -1. REGIMEN D: Patients receive cyclophosphamide IV on days -6 and -5 and TBI BID on days -3 to -1. REGIMEN E: Patients receive TBI QD on days -7 to -4 and etoposide IV on day -3. REGIMEN F: Patients receive TBI BID on days -6 to -4 and etoposide IV on day -3. ALLOGENEIC STEM CALL TRANSPLANTATION: Patients undergo allogeneic stem cell transplantation on day 0. GRAFT-VS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive 1 of the following regimens: REGIMEN A: Patients receive sirolimus PO and tacrolimus IV continuously (changing to PO BID) beginning on day -3 and continuing for 6 months. REGIMEN B: Patients receive tacrolimus IV continuously (changing to PO BID) and continuing for 6 months, and methotrexate IV on days 1, 3, 6, and 11. SINGLE-AGENT THERAPY: After completion of maintenance therapy or beginning on day 100 post-transplantation, patients receive dasatinib PO QD for up to 5 years. After completion of study therapy, patients are followed every 6 months for up to 5 years.