Trial Information

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.

PROJECTED ACCRUAL: A total of 26-45 lymphoma patients and 2-6 leukemia patients will be
accrued for this study.