RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Zosuquidar trihydrochloride may help daunorubicin and cytarabine kill more cancer cells by making cancer cells more sensitive to the drugs. It is not yet known whether daunorubicin and cytarabine are more effective with or without zosuquidar trihydrochloride in treating acute myeloid leukemia or anemia.

PURPOSE: This randomized phase III trial is studying how well giving zosuquidar trihydrochloride together with daunorubicin and cytarabine works compared to daunorubicin and cytarabine alone in treating older patients with newly diagnosed acute myeloid leukemia or anemia that has not responded to previous treatment.

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.

• Leukemia
• Myelodysplastic Syndromes

• Biological: filgrastim
• Biological: sargramostim
• Drug: cytarabine
• Drug: daunorubicin hydrochloride
• Drug: zosuquidar trihydrochloride

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