• Comparison of disease-free and overall survival [ Designated as safety issue: No ]
  

• Toxicity [ Designated as safety issue: Yes ]
  

OBJECTIVES:

• Compare the effect of induction chemotherapy with or without PSC 833 (induction chemotherapy [arm II] closed to accrual as of 8/11/03) on disease-free survival and overall survival in patients with previously untreated acute myeloid leukemia.
• Determine whether post-consolidation immunotherapy with low-dose interleukin-2 (IL-2) and continuous/intermittent high-dose IL-2 improves disease-free survival and overall survival in patients who achieve first complete remission.
• Determine the effectiveness of three courses of high-dose cytarabine (HiDAC) to cure patients with core-binding factor leukemias.
• Determine the feasibility and efficacy of intensive post-remission chemotherapy using peripheral blood stem cell transplantation or a novel intensification sequence of HiDAC/high-dose etoposide/filgrastim (G-CSF) followed by two courses of HiDAC in patients with unfavorable cytogenetics in complete remission.

OUTLINE: This is a randomized, multicenter study.

• Induction Therapy:Patients are randomized to 1 of 2 treatment arms. (Arm II closed to accrual as of 8/11/03.)

  • Arm I: Patients receive cytarabine IV continuously on days 1-7 and daunorubicin IV over 5-10 minutes followed by etoposide IV over 2 hours on days 1-3. Patients with 20% or greater bone marrow cellularity and greater than 5% leukemia blasts at the end of the first course receive a second course of cytarabine IV continuously on days 1-5 and daunorubicin IV over 5-10 minutes followed by etoposide IV over 2 hours on days 1 and 2.
  • Arm II (closed to accrual as of 8/11/03): Patients receive PSC 833 IV continuously on days 1-3 and cytarabine, daunorubicin, and etoposide as in arm I. Patients with 20% or greater bone marrow cellularity and greater than 5% leukemia blasts at the end of the first course receive a second course of PSC 833 IV continuously on days 1 and 2 and cytarabine, daunorubicin, and etoposide as in arm I.

• Intensification Therapy: Patients in complete remission receive intensification therapy. Therapy begins no earlier than 2 weeks and no later than 4 weeks after complete remission is attained. Patients are stratified according to cytogenetics (favorable [t(8;21)(q22;q22) or inv(16)(p13;q22) or t(16;16)(p13;q22)] vs unfavorable [all other karyotypes]).

  • Favorable: Patients receive high-dose cytarabine (HiDAC) IV over 3 hours every 12 hours on days 1, 3, and 5. Treatment repeats no earlier than 28 days after the prior course and no later than 14 days after hematopoietic recovery for two more courses.

  • Unfavorable: Patients are further divided into two groups based on ability to receive peripheral blood stem cell transplantation (PBSCT) (yes vs no).

    • PBSCT group: Patients receive etoposide IV continuously and HiDAC IV over 2 hours every 12 hours on days 1-4. Patients also receive filgrastim (G-CSF) subcutaneously (SC) daily beginning on day 14 and continuing until peripheral blood stem cell (PBSC) collection is completed. Patients who are not able to undergo PBSCT after HiDAC/etoposide continue treatment in the non-PBSCT group. At least 4 weeks after HiDAC/etoposide recovery, patients receive oral busulfan every 6 hours on days -7 to -4 and etoposide IV over 4 hours on day -3 prior to PBSCT. Patients receive autologous PBSC infusion on day 0. Patients also receive G-CSF SC beginning on day 0 and continuing until hematopoietic recovery.
    • Non-PBSCT group: Patients receive etoposide, HiDAC, and G-CSF as in the PBSCT group. After hematopoietic recovery, patients then receive HiDAC IV over 3 hours every 12 hours on days 1, 3, and 5. Treatment repeats no earlier than 28 days after prior course and no later than 14 days after hematopoietic recovery for one more course.

• Immunotherapy: Patients are again randomized to 1 of 2 treatment arms.

  • Arm I: Patients begin therapy no later than 120 days after the first day of the last course of HiDAC treatment OR day 0 of PBSCT. Patients receive low-dose interleukin-2 (IL-2) SC on days 1-14, 19-28, 33-42, 47-56, 61-70, and 75-90. In addition, patients receive high-dose IL-2 SC on days 15-17, 29-31, 43-45, 57-59, and 71-73.
  • Arm II: Patients are observed and receive no further therapy. Patients are followed at 1 month, every 2 months for 2 years, every 6 months for 2 years, and then annually for 6 years.

PROJECTED ACCRUAL: A total of 720 patients will be accrued for this study within 4 years.