PRIMARY OBJECTIVES:~I. To evaluate the clinical efficacy (event-free survival) of an intensive short-term chemotherapy regimen (hyperfractionated cyclophosphamide-vincristine sulfate-Adriamycin [doxorubicin hydrochloride]-dexamethasone [hyper-CVAD] program) given in combination with the tyrosine kinase inhibitor ponatinib hydrochloride (ponatinib) for Philadelphia (Ph)-positive and/or BCR-ABL-positive acute lymphoblastic leukemia (ALL).~II. To evaluate other clinical efficacy endpoints (overall response rate and survival) and safety of the regimen.~OUTLINE:~ODD CYCLES (1, 3, 5, and 7): Patients receive cyclophosphamide intravenously (IV) over 3 hours every 12 hours on days 1-3, doxorubicin hydrochloride IV continuously over 24 hours on day 4, vincristine sulfate IV over 30 minutes on days 1 and 11, dexamethasone IV over 30 minutes or orally (PO) once daily (QD) on days 1-4 and 11-14, and ponatinib hydrochloride PO QD on days 1-14 of cycle 1 and continuously in cycles 3, 5, and 7. Patients with CD20 expression may also receive rituximab IV on days 1 and 11 of cycle 1 and 3. Treatment repeats every 3-4 weeks for up to 8 cycle in the absence of disease progression or unacceptable toxicity.~EVEN CYCLES (2, 4, 6, and 8): Patients receive methotrexate IV over 24 hours on day 1, ponatinib hydrochloride PO QD continuously, and cytarabine IV over 3 hours every 12 hours on days 2 and 3. Patients with CD20 expression may also receive rituximab IV on days 1 and 8 of cycle 2 and 4. Treatment repeats every 3-4 weeks for up to 8 cycle in the absence of disease progression or unacceptable toxicity.~MAINTENANCE THERAPY: Patients receive vincristine sulfate IV on day 1, prednisone PO daily on days 1-5, and ponatinib hydrochloride PO QD on days 1-28. Cycle repeat every 28 days for 24 months in the absence of disease progression or unacceptable toxicity.~After completion of study treatment, patients are followed up at 30 days and then every 6 months for up to 24 months.
This phase II trial studies the side effects and how well combination chemotherapy and ponatinib hydrochloride work in treating patients with acute lymphoblastic leukemia. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ponatinib hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy and ponatinib hydrochloride may be an effective treatment for acute lymphoblastic leukemia.