HIGH INTENSITY, BRIEF DURATION CHEMOTHERAPY FOR DIFFUSE SMALL NONCLEAVED CELL LYMPHOMA AND THE L-3 SUBTYPE OF ALL: A PILOT STUDY OF A MULTIDRUG REGIMEN

OBJECTIVES: I. Determine the response rate and disease free survival of HIV seronegative patients with diffuse small noncleaved cell lymphoma or L3 acute lymphocytic leukemia when treated with high intensity, brief duration combination chemotherapy: alternating courses of ifosfamide/cytarabine/etoposide and cyclophosphamide/doxorubicin, each with methotrexate/vincristine/dexamethasone. II. Determine the toxicity of these regimens in HIV negative patients. OUTLINE: Patients are stratified by participating institution and disease type (diffuse small noncleaved cell lymphoma vs L3 ALL). Patients receive cyclophosphamide IV over 5-10 minutes on days 1 through 5 and oral prednisone on days 1 through 7, followed by alternating courses of: 2) ifosfamide IV over 1 hour on days 8 through 12, methotrexate IV over 24 hours on day 8; leucovorin calcium IV over 36 hours after initiation of methotrexate, then IV (or orally as tolerated, after the first 24 hours) every 6 hours until the serum methotrexate level is below 5 x 10 to the minus eighth M; vincristine IV on day 8; cytarabine IV over 48 hours and etoposide IV over 60 minutes on days 11 and 12; and oral dexamethasone on days 8 through 12, plus triple intrathecal therapy (TIT) with methotrexate, cytarabine, and hydrocortisone on days 8 and 12, and 3) cyclophosphamide IV over 5-10 minutes on days 29 through 33; methotrexate IV over 24 hours and vincristine IV on day 29; leucovorin calcium IV over 36 hours after initiation of methotrexate, then IV (or orally as tolerated, after the first 24 hours) every 6 hours until the serum methotrexate level is below 5 x 10 to the minus eighth M; doxorubicin IV on days 32 and 33; and oral dexamethasone on days 29 through 33, plus TIT on day 29, with doses as above. Patients with CNS disease at diagnosis continue TIT once weekly until the CSF clears, then weekly for 4 more weeks. TIT must be completed prior to initiation of radiotherapy. All patients must complete at least the first 3 courses of chemotherapy. Courses 2 and 3 each repeat 3 times in the absence of disease progression or unacceptable toxicity. On days 134-139, patients who have had prior bone marrow involvement receive cranial radiation therapy. Patients who achieve less than a complete response and who have an HLA-matched sibling should undergo allogeneic bone marrow transplant on protocol CLB-9113. Patients are followed monthly for 6 months, every 2 months for 18 months, every 6 months for 2 years, and thereafter for survival.