A Multicenter Study to Assess the Efficacy of 506U78 in Patients With Chronic Lymphocytic Leukemia Who Are Refractory to Fludarabine and Alkylator Therapy

Inclusion Criteria

DISEASE CHARACTERISTICS: Diagnosis of refractory chronic lymphocytic leukemia Evidence of
active disease after fludarabine or alkylator therapy Must meet one or more of the
following criteria for active disease: Minimum of one of the following disease-related
symptoms: Weight loss of 10% or more within the previous 6 months Extreme fatigue (e.g.,
unable to work or perform usual activities) Fevers greater than 100.5 degrees F for 2
weeks or more without evidence of infection Night sweats without evidence of infection
Evidence of progressive marrow failure manifested by the development or worsening of
autoimmune anemia and/or thrombocytopenia that is poorly responsive to corticosteroid
therapy Massive (e.g., greater than 6 cm below the left costal margin) or progressive
splenomegaly Massive nodes or clusters (e.g., greater than 10 cm in longest diameter) or
progressive lymphadenopathy Progressive lymphocytosis with an increase of more than 50%
over a 2-month period or an anticipated doubling time of less than 6 months Ineligible if
marked hypogammaglobulinemia or development of monoclonal protein in the absence of the
above criteria for active disease Must have one of the following resulting from prior
fludarabine or alkylator-containing therapy: Disease progression during therapy Failure to
respond or obtained less than a partial response to therapy Disease progression within 6
months of the last course of therapy after an initial response Failure to respond or
disease progression allowed at any time after the final dose if alkylator agent was not
the most recent therapy

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 60-100% Life
expectancy: At least 12 weeks Hematopoietic: See Disease Characteristics Hepatic: See
Disease Characteristics Bilirubin no greater than 2 times upper limit of normal No liver
dysfunction due to organ infiltration by lymphocytes Renal: Creatinine clearance at least
50 mL/min Other: Not pregnant or nursing Negative pregnancy test Fertile patients must use
effective contraception during and for up to 28 days after study No neurotoxicity of grade
2 or higher No history of significant neurologic toxicity (grade 2 or greater motor or
sensory impairment) due to prior chemotherapy or radiotherapy No history of seizure
disorder No active infection No other malignancy within the past 2 years (except
adequately treated non- melanomatous skin cancer or carcinoma in situ) that would preclude
study No systemic nonmalignant comorbid disease that would preclude study No
psychological, sociological, or geographical condition that would preclude study

PRIOR CONCURRENT THERAPY: Biologic therapy: No prior bone marrow or peripheral blood stem
cell transplantation Recovered from prior immunotherapy At least 4 weeks since prior
biologic therapy and recovered Concurrent growth factors allowed Chemotherapy: See Disease
Characteristics At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or
mitomycin) and recovered No prior 506U78 therapy No other concurrent chemotherapy
Endocrine therapy: See Disease Characteristics No concurrent corticosteroid therapy
greater than 10 mg/day of prednisone equivalent No concurrent corticosteroids as
antiemetics Concurrent hormone replacement therapy or oral contraceptives allowed
Concurrent hydrocortisone as prophylaxis or treatment of transfusion reactions allowed
Radiotherapy: At least 4 weeks since prior radiotherapy and recovered No concurrent
radiotherapy Surgery: Not specified Other: No other concurrent anticancer agents