Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Properties of Oral AT-406 in Combination With Daunorubicin and Cytarabine in Patients With Poor-risk Acute Myelogenous Leukemia (AML)

This is an open label, multi-center, dose escalation study to determine the MTD of oral
AT-406 combined with daunorubicin and cytarabine in patients with poor-risk AML. Treatment
with AT-406 will be administered to up to 60 patients at approximately 7 investigational
sites in the US. Patients will be enrolled in open label sequential cohorts of up to 12
patients to determine the MTD of AT-406 in combination with daunorubicin and cytarabine.
Dose finding will occur during the induction cycle of the regimen. AT-406 will not be
administered in consolidation cycles. Patients who require re-induction during initial
treatment will be removed from the study and replaced (if needed) in order to assess at
least 3 evaluable patients at each dose level.

Clinical and laboratory parameters will be assessed to evaluate the toxicity of AT-406. In
addition, pharmacokinetic (PK) and pharmacodynamic (PDy) blood samples will be analyzed for
plasma concentrations and PDy effect of AT-406, respectively.

Eligibility Criteria:

Inclusion:

- Male or females patients ages 18 to 74

- Morphological diagnosis of untreated or relapsed non-M3 AML according to WHO
diagnostic criteria who exhibit at least one poor-risk feature and are not be known
to exhibit any favorable cytogenetic features or variants.

- Patients with relapsed AML and patients with prior autologous or allogeneic
hematopoietic stem cell transplantations are eligible if relapse occurred following a
remission of ≥ 6 months.

- Patients must have an ECOG score of ≤ 2,

- Adequate cardiac, liver and renal function.

Exclusion:

- Must not have any evidence of CNS leukemia.