This phase II trial studies how well combination chemotherapy with or without rituximab, imatinib mesylate, dasatinib, or ruxolitinib works in treating patients with newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma. Drugs used in chemotherapy 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. Monoclonal antibodies, such as rituximab, may interfere with the ability of cancer cells to grow and spread. Imatinib mesylate, dasatinib, and ruxolitinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving combination chemotherapy together with rituximab, imatinib mesylate, dasatinib, or ruxolitinib may be an effective treatment for patients with acute lymphoblastic leukemia or lymphoblastic lymphoma.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT01319981.
PRIMARY OBJECTIVES:
I. To determine the complete remission (CR) rate at 1 year of hyperfractionated (hyper) cyclophosphamide, liposomal vincristine sulfate, doxorubicin hydrochloride, and dexamethasone (CVAD) with liposomal vincristine (Marqibo) (liposomal vincristine sulfate) in newly diagnosed acute lymphoblastic leukemia (ALL).
II. To determine CR duration, toxicity and overall survival of hyper CVAD with liposomal vincristine (Marqibo) in newly diagnosed ALL.
OUTLINE:
COURSES 1, 3, 5, 7: Patients receive rituximab intravenously (IV) on days 1 and 8 (courses 1 and 3 only) (CD20+ patients), imatinib mesylate orally (PO) daily, dasatinib PO daily, or ruxolitinib PO twice daily (BID) on days 1-14 of course 1 and continuously thereafter (Philadelphia chromosome positive [Ph]+ patients or Ph-like disease), cyclophosphamide IV over 3 hours approximately every 12 hours on days 1-3, doxorubicin hydrochloride IV over 24 hours on day 4, liposomal vincristine sulfate IV over 1 hour on days 1 and 8, and dexamethasone IV or PO daily on days 1-4 and 11-14.
COURSES 2, 4, 6, 8: Patients receive rituximab IV on days 1 and 8 (courses 2 and 4 only) (CD20+ patients), imatinib mesylate PO daily, dasatinib PO daily, or ruxolitinib PO BID (Ph+ patients or Ph-like disease), methotrexate IV over 24 hours on day 1, methylprednisolone IV approximately every 12 hours on days 1-3, and cytarabine IV over 2 hours approximately every 12 hours on days 2-3.
Treatment repeats every 21-28 days for up to 8 courses in the absence of disease progression or unacceptable toxicity. Patients then begin maintenance therapy and intensive chemotherapy consolidation.
MAINTENANCE THERAPY:
NON-PH+ PATIENTS: Patients receive mercaptopurine PO daily, methotrexate IV or PO once weekly, liposomal vincristine sulfate IV over 1 hour on day 1, and dexamethasone PO on days 1-5. Courses repeat every month in the absence of disease progression or unacceptable toxicity.
PH+ PATIENTS OR PH-LIKE DISEASE: Patients receive imatinib mesylate PO daily, dasatinib PO daily, or ruxolitinib PO BID, liposomal vincristine sulfate IV over 1 hour on day 1, and dexamethasone PO on days 1-5. Courses repeat every month in the absence of disease progression or unacceptable toxicity.
INTENSIVE CHEMOTHERAPY CONSOLIDATION:
NON-PH+ PATIENTS: Six months after beginning maintenance therapy, patients receive cyclophosphamide, liposomal vincristine sulfate, doxorubicin hydrochloride, and dexamethasone as in course 1 during month 6. Patients then receive methotrexate IV on day 1 and pegaspargase IV over 2 hours on day 2. Treatment with methotrexate and pegaspargase repeats weekly for 4 weeks during month 7. Intensive chemotherapy consolidation is repeated at 18 months after patients begin maintenance therapy.
PH+ PATIENTS OR PH-LIKE DISEASE: Six months after beginning maintenance therapy, patients receive cyclophosphamide, liposomal vincristine sulfate, doxorubicin hydrochloride, and dexamethasone as in course 1 during month 6. Patients with CD20+ disease may also receive rituximab. Intensive chemotherapy consolidation is repeated at 18 months after patients begin maintenance therapy.
Lead OrganizationM D Anderson Cancer Center
Principal InvestigatorElias Jabbour
