• Identify zosuquidar dose and schedule during induction that will achieve at least a minimum threshold plasma level of 170 ng/mL prior to first administration of daunorubicin, and which is sustained for the remaining 68 hours of zosuquidar infusion.
• Evaluate the tolerablility of this induction regimen for newly diagnosed AML in older patients.

• Assess P-glycoprotien (P-gp) expression and function by flow cytometry in leukemia cells at study entry.
• Assess effect of zosuquidar on the pharmacodynamic endpoint of P-gp inhibition in CD56+ natural killer cells obtained from patients during induction.
• Assess the pharmacokinetics of daunorubicin and its metabolite daunorubicinol during induction.
• Observe complete remission rate, leukemia-free survival (LFS) and overall survival (OS).

Chemotherapy drugs use different ways to stop cancer cells from dividing so they stop growing or die. Zosuquidar 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 in treating acute myeloid leukemia.

Purpose:

Phase I:

To Evaluate the safety of different doses of zosuquidar.

Phase II:

This study is designed to study the safety and effectiveness of zosuquidar when given with daunorubicin and cytarabine in newly diagnosed AML patients.

• Drug: Zosuquidar
• Drug: Daunorubicin
• Drug: Cytarabine

Inclusion Criteria:

• Newly diagnosed acute myeloid leukemia
• Ages 55-75 years

Exclusion Criteria:

• Acute promyelocytic leukemia (FAB M3)
• Patients must not have received prior chemotherapy for AML.
• Prior exposure to anthracycline
• Use of any investigational agent within 4 weeks prior to enrollment into the study

For Phase II:

• Patients must be P-glycoprotein positive