OBJECTIVES:

• Compare the overall survival and progression-free survival of elderly patients with newly diagnosed acute myeloid leukemia, refractory anemia with excess blasts (RAEB) in transformation, or high-risk RAEB treated with daunorubicin and cytarabine with or without zosuquidar trihydrochloride.
• Compare the complete remission rate of patients treated with these regimens.
• Compare the toxicity of these regimens in these patients.
• Compare the systemic exposure of daunorubicin and cytarabine in patients treated with zosuquidar trihydrochloride vs placebo.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to age (60-69 years vs 70 years and over), disease (refractory anemia with excess blasts [RAEB] vs RAEB in transformation or acute myeloid leukemia [AML]), and disease type (de novo vs secondary). Patients are randomized to 1 of 2 treatment arms.

• Induction:

  • Arm I: Patients receive daunorubicin IV over 10-15 minutes and zosuquidar trihydrochloride IV over 6 hours on days 1-3. Patients also receive cytarabine IV continuously on days 1-7.
  • Arm II: Patients receive daunorubicin and cytarabine as in arm I. Patients also receive placebo IV over 6 hours on days 1-3.

Beginning on day 12, patients who achieve aplasia receive filgrastim (G-CSF) or sargramostim (GM-CSF) subcutaneously (SC) or IV daily until blood counts recover. Patients who have evidence of persistent AML are eligible to receive a second identical course of induction chemotherapy.

• Consolidation I (beginning within 8 weeks after documentation of complete remission [CR] or measurable remission [MR]): Patients who achieve a CR or MR receive cytarabine IV over 1 hour once or twice daily on days 1-6 and GM-CSF or G-CSF SC or IV beginning on day 7 and continuing until blood counts recover.
• Consolidation II: Patients who have maintained peripheral blood evidence of a remission receive daunorubicin, cytarabine, and zosuquidar trihydrochloride or placebo as in induction chemotherapy. Patients also receive GM-CSF or G-CSF SC or IV beginning on day 8 or after last cytarabine dose and continuing until blood counts recover.

Patients are followed monthly for 1 year, every 2 months for 1 year, every 3 months for 1 year, and then every 6 months for 2 years.

PROJECTED ACCRUAL: Approximately 450 patients (225 per treatment arm) will be accrued for this study within 4.1 years.

DISEASE CHARACTERISTICS:

• Histologically confirmed newly diagnosed acute myeloid leukemia (AML), refractory anemia with excess blasts (RAEB) in transformation (RAEB-T), or high-risk RAEB

  • AML with 30% myeloblasts on bone marrow aspirate or peripheral blood differential

    • Any FAB subtype except M3 (i.e., acute promyelocytic leukemia)
  • RAEB with 11-20% myeloblasts on bone marrow aspirate or peripheral blood differential, provided there are other criteria for high-risk disease
  • RAEB-T with 21-30% myeloblasts on bone marrow aspirate or peripheral blood differential
• No blastic transformation of chronic myelogenous leukemia
• Secondary AML allowed
• No CNS leukemia

PATIENT CHARACTERISTICS:

Age

• Over 60

Performance status

• ECOG 0-3

Life expectancy

• Not specified

Hematopoietic

• See Disease Characteristics

Hepatic

• Bilirubin no greater than 3 mg/dL

Renal

• Creatinine less than 2 mg/dL

Cardiovascular

• Ejection fraction at least 45% by MUGA or 2-dimensional echocardiogram

Other

• No other malignancy for which patient is concurrently receiving treatment
• Not pregnant or nursing
• Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY:

Biologic therapy

• No other concurrent colony-stimulating factors (e.g., epoetin alfa)

Chemotherapy

• No prior chemotherapy for AML except hydroxyurea

Endocrine therapy

• Not specified

Radiotherapy

• Not specified

Surgery

• Not specified