Trial Information

Phase III Study of MDR Modulation With PSC-833 (NSC #648265) Followed by Immunotherapy With rIL-2 (NSC #373364) vs. No Further Therapy in Previously Untreated Patients With AML >60 Years

PRIMARY OBJECTIVES:

I. To determine whether the addition of PSC-833 to induction chemotherapy improves complete
response rates and whether the addition of PSC-833 to induction and consolidation
chemotherapy improves survival for patients with AML >= 60 years.

II. To determine whether the administration of low-dose, subcutaneous rIL-2 immunotherapy
with intermittent high-dose boluses after chemotherapy prolongs disease-free survival.

OUTLINE: This is a partially randomized, multicenter study. Patients are stratified
according to participating center and disease characteristics (de novo acute myeloid
leukemia (AML) versus AML with antecedent myelodysplasia). Patients are randomized to one of
two maintenance therapy arms.

Arm I: Patients receive cytarabine IV continuously over 7 days and daunorubicin IV bolus
followed by etoposide IV over 2 hours on days 1-3.

Arm II: Patients receive treatment as in arm I with the addition of PSC 833 induction. A
loading dose of PSC 833 IV is given over 2 hours, followed by a 74-hour continuous infusion
of PSC 833 beginning 2 hours before daunorubicin and etoposide. Patients may receive a
second induction course if residual leukemia is present in the bone marrow. Patients who
experience a complete remission (CR) and meet certain other criteria receive postremission
chemotherapy consisting of cytarabine IV continuously over 5 days plus daunorubicin IV
followed by etoposide IV over 2 hours on days 1 and 2. Patients who are randomized to
receive PSC 833 during induction chemotherapy receive a loading dose of PSC 833 before
beginning a 48-hour continuous infusion of PSC 833 concurrently with
cytarabine/daunorubicin/etoposide postremission chemotherapy.

After completing postremission chemotherapy, patients are randomized to a no further
treatment group or interleukin-2 (IL-2) immunotherapy. Treatment begins within 5 months of
postremission chemotherapy. IL-2 immunotherapy consists of low-dose subcutaneous (SC) IL-2
on days 1-14, 19-28, 33-42, 47-56, 61-70, and 75-90 and high-dose bolus SC IL-2 on days
15-17, 29-31, 43-45, 57-59, and 71-73.

Patients are followed every 2 months for 2 years, every 6 months for 2 years, annually until
the tenth year, and then at relapse.