A PHASE II STUDY OF COMPOUND 506U78 IN PATIENTS WITH REFRACTORY T-CELL MALIGNANCIES - POG/CCG Intergroup Study
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
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
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.
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Early marrow CR plus PR rate at day 21
CR is defined by an M1 marrow which requires blast counts below 5%. PR is defined by an M2 marrow which requires blast counts below 25%.
Swiss Pediatric Oncology Group - Geneva
United States: Food and Drug Administration