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.