ACUTE MYELOID LEUKAEMIA TRIAL 12

OBJECTIVES:

• Compare the remission rate, duration of remission, survival, toxicity, and supportive care requirements associated with induction chemotherapy with cytarabine, daunorubicin, and etoposide vs mitoxantrone, cytarabine, and etoposide in patients with acute myeloid leukemia.
• Assess filgrastim (G-CSF) support in the recovery phase after the first induction course with respect to remission rate, reasons for failure, hematologic regeneration, febrile incidents, supportive care requirements, and overall survival in these patients.
• Compare 4 vs 5 courses of total treatment, with either chemotherapy or bone marrow transplantation (BMT) as the final course, with respect to remission duration, relapse rate, disease free mortality, and overall survival in these patients.
• Compare allogeneic or autologous BMT vs conventional chemotherapy with respect to remission duration, relapse rate, disease free mortality, and overall survival in these patients.
• Evaluate the prognostic significance of blood and bone marrow morphology, cytogenetics, molecular genetics, and immunophenotype assessed at diagnosis, at second randomization, and at relapse.

OUTLINE: This is a randomized study. Patients are stratified by center, age (15-29 vs 30-39 vs 40-49 vs 50-59), performance status, and disease status (de novo vs secondary). Patients who are eligible for the second randomization are also stratified by first randomization treatment (arm I vs II) and prognostic risk group (good vs standard).

Original first randomization (closed as of 11/1998): Patients are randomized to 1 of 2 induction treatment arms.

• Arm I: During course 1, patients receive cytarabine IV every 12 hours on days 1-10, daunorubicin IV on days 1, 3, and 5, and etoposide IV over 1 hour on days 1-5. Patients are further randomized to receive either filgrastim (G- CSF) or placebo subcutaneously (SQ) beginning on day 18 and continuing until 2 days after blood counts have recovered (G-CSF randomization closed as of 8/15/2000). During course 2, patients receive daunorubicin and etoposide as in course 1 and cytarabine IV every 12 hours on days 1-8, but no G-CSF or placebo unless peripheral blood stem cells (PBSC) are harvested.
• Arm II: During course 1, patients receive mitoxantrone IV on days 1, 3, and 5 and cytarabine, etoposide, and G-CSF or placebo as in course 1 of arm I. During course 2, patients receive mitoxantrone and etoposide as in course 1 of arm II, cytarabine as in course 2 of arm I, but no G-CSF or placebo unless PBSC are harvested.