RATIONALE: Some cancers become resistant to chemotherapy drugs. Combining PSC 833 with more than one chemotherapy drug may reduce resistance to the drugs and allow the cancer cells to be killed. Combining interleukin-2 with combination chemotherapy plus PSC 833 may kill more cancer cells.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with or without PSC 833 followed by interleukin-2 or no further therapy in treating older patients who have acute myeloid leukemia.

OBJECTIVES: I. Determine whether the addition of PSC 833 to induction chemotherapy improves the complete response rate of patients with acute myeloid leukemia (PSC 833 treatment arm closed as of 8/15/99). II. Determine whether the addition of PSC 833 to induction and consolidation chemotherapy improves survival in this patient population (PSC 833 treatment arm closed as of 8/15/99). III. Determine whether the administration of low-dose and intermittent high- dose interleukin-2 after chemotherapy prolongs disease-free survival in this patient population.

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: (Closed as of 8/15/99) 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.

PROJECTED ACCRUAL: Approximately 640 patients will be accrued for this study within 4 years.

• Biological: aldesleukin
• Drug: cytarabine
• Drug: daunorubicin hydrochloride
• Drug: etoposide

• Baer MR, George SL, Caligiuri MA, Sanford BL, Bothun SM, Mrózek K, Kolitz JE, Powell BL, Moore JO, Stone RM, Anastasi J, Bloomfield CD, Larson RA. Low-Dose Interleukin-2 Immunotherapy Does Not Improve Outcome of Patients Age 60 Years and Older With Acute Myeloid Leukemia in First Complete Remission: Cancer and Leukemia Group B Study 9720. J Clin Oncol. 2008 Jun 30; [Epub ahead of print]
• Baer MR, George SL, Dodge RK, O'Loughlin KL, Minderman H, Caligiuri MA, Anastasi J, Powell BL, Kolitz JE, Schiffer CA, Bloomfield CD, Larson RA. Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood. 2002 Aug 15;100(4):1224-32.
• Kolitz JE, George SL, Baer MR, Lee EJ, Bloomfield CD, Larson RA; Cancer and Leukemia Group B (CALGB) trials in younger and older adults. P-glycoprotein (Pgp) modulation in untreated acute myeloid leukemia (AML): Cancer and Leukemia Group B (CALGB) trials in younger and older adults. Ann Hematol. 2004;83 Suppl 1:S103-4. No abstract available.
• Sekeres MA, Peterson B, Dodge RK, Mayer RJ, Moore JO, Lee EJ, Kolitz J, Baer MR, Schiffer CA, Carroll AJ, Vardiman JW, Davey FR, Bloomfield CD, Larson RA, Stone RM; Cancer and Leukemia Group B. Differences in prognostic factors and outcomes in African Americans and whites with acute myeloid leukemia. Blood. 2004 Jun 1;103(11):4036-42. Epub 2004 Feb 19.

DISEASE CHARACTERISTICS: Histologically confirmed acute myeloid leukemia (AML), all FAB except M3 (acute promyelocytic leukemia) History of antecedent myelodysplasia allowed No prior treatment for AML or myelodysplasia except: Emergency leukapheresis Emergency treatment for hyperleukocytosis with hydroxyurea Single-dose cranial radiotherapy for CNS leukostasis Growth factor/cytokine support

PATIENT CHARACTERISTICS: Age: 60 and over Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: Not specified Renal: Not specified Other: Not pregnant or nursing Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics Chemotherapy: See Disease Characteristics No other concurrent chemotherapy Endocrine therapy: No concurrent hormonal therapy except for nondisease-related conditions (e.g., insulin for diabetes or estrogens or progestins for gynecologic conditions) No concurrent steroids (including as antiemetics) except for adrenal failure or septic shock Radiotherapy: See Disease Characteristics No concurrent palliative radiotherapy Surgery: Not specified Other: No concurrent medications that interact with cyclosporine