506U78 in Treating Patients With Refractory Hematologic Cancer

OBJECTIVES:

I. Determine the response rate to compound 506U78 (2-amino-9-b-D-arabinofuranosyl-6-methoxy-9H-purine) administered as a 1 hour infusion daily for 5 days in patients with recurrent T-cell malignancies.

II. Determine the toxicities of compound 506U78 in this group of patients. III. Correlate the biochemical pharmacology of compound 506U78 (e.g., ara-G nucleotides in leukemic blasts and CSF concentrations) with clinical response.

IV. Determine the impact of compound 506U78 therapy on survival and duration of response of patients with recurrent T-cell malignancies.

OUTLINE: Patients are stratified according to disease characteristics: Group 1: T-cell ALL or NHL in first relapse (greater than 25% bone marrow blasts, with or without concomitant extramedullary relapse other than CNS); Group 2: T-cell ALL or NHL in second or later relapse (greater than 25% bone marrow blasts, with or without concomitant extramedullary relapse other than CNS); Group 3: T-cell ALL or NHL with positive bone marrow and CSF (greater than 5% bone marrow blasts and CNS 2 or 3 involvement); Group 4: Extramedullary relapse and less than 25% blasts in the bone marrow (excluding isolated CNS relapse)

GROUP 1: Patients receive a 1 hour infusion of compound 506U78 daily for 5 days in the absence of neurologic toxicity. The course repeats every 21 days. If a first relapse T-cell ALL study of higher priority is not open, then the patient may continue to receive the drug every 21 days for a maximum of 2 years provided that the patient has achieved a second complete response.

GROUPS 2 and 4: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. After 3 courses a patient may be given CNS prophylaxis with triple intrathecal therapy (TIT), consisting of methotrexate, cytarabine and hydrocortisone after consultation with study coordinator. TIT should be given every 12 weeks.

GROUP 3: Patients receive compound 506U78 every 21 days for a maximum of 2 years, in the absence of disease progression. TIT will be given on day 1 of weeks 1-4, 6, 9 and every 6 weeks for 12 weeks, and then every 9 weeks thereafter. This stratum is open.

Inclusion criteria

• Refractory or recurrent acute lymphocytic leukemia (ALL) or non-Hodgkin's lymphoma (NHL) with bone marrow involvement (T-cell disease only)
• Isolated CNS relapse not eligible
• Performance status - Karnofsky 50-100%
• At least 8 weeks
• Bilirubin no greater than 1.5 mg/dL
• SGPT less than 5 times normal
• Creatinine normal for age
• Creatinine clearance or GFR at least 60 mL/min/1.73m2
• No severe uncontrolled infection
• No concurrent biologic therapy
• Recovered from toxic effects
• At least 6 weeks from administration of nitrosoureas
• No concurrent endocrine therapy
• At least 6 weeks from administration of craniospinal or hemi pelvic radiotherapy