AEG35156 in Combination With High-dose Cytarabine and Idarubicin in AML Following Failure of a Single Standard Dose Cytarabine Based Frontline Induction Regimen

An Open-Label Randomized Phase 2 Study of the X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 Given in Combination With High-dose Cytarabine and Idarubicin in AML Following Failure of a Single Standard Dose Cytarabine Based Frontline Induction Regimen

To determine if AEG35156 can enhance the combined complete remission (CR) and CR with incomplete platelet recovery (CRp) rate of high-dose cytarabine and idarubicin in AML following failure of a single standard dose cytarabine based frontline induction regimen.

Inclusion Criteria:

• Patients with AML, except those with APL (acute promyelocytic leukemia), failing a single standard dose cytarabine based frontline induction regimen. The diagnosis of refractory AML is based on the presence of either > 10% blasts in marrow or blood or 5-10% blasts in either site together with cytopenia (Hb < 10 g/dL, or platelets < 100 x 109/L, or neutrophil count < 1.0 x 109/L).
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
• Male, or female patients who are post-menopausal (amenorrheic for at least 12 months), or surgically or biologically sterile.
• Patients must have adequate organ and immune function as indicated by the following laboratory values:

Parameter Laboratory Values Serum creatinine; ≤2.0 mg/dL (≤ 177 μmol/L Total Bilirubin ≤2.0 mg/dL (≤ 34 μmol/L) AST (SGOT) and ALT (SGPT) ≤3 X ULN

• The patient must understand, be able and willing and likely to fully comply with study procedures, including scheduled follow-up, and restrictions.

Exclusion Criteria:

• Clinical evidence of ongoing grade 3 or 4 non-hematological toxicities from the initial standard dose cytarabine-based induction chemotherapy
• Patients with a prior history of peripheral neuropathy of grade 2 or higher.
• Clinical evidence of active CNS leukemic involvement.
• Active and uncontrolled infection. Patients with an infection who are under active treatment with antibiotics and whose infections are controlled may be entered to the study.
• Current evidence of invasive fungal infection (blood or tissue culture).
• Current evidence of an active second malignancy except for non-melanoma skin cancer.
• Uncontrolled medical problems, unrelated to the malignancy, or of sufficient severity that in the opinion of the investigator, impair a patient's ability to give informed consent or unacceptably reduce the safety of the proposed treatment.
• Neurological or psychiatric disorders that would interfere with consent or study follow-up.
• Known or suspected intolerance or hypersensitivity to the study drugs [or closely related compounds] or any of their stated ingredients. Study drugs being the antisense, cytarabine and idarubicin.
• History of alcohol or other substance abuse within the last year.
• Use of another investigational agent within the last 14 days prior to enrolment. Patients who have received a previous antisense agent in the last 90 days will be excluded.
• Female patients who are pregnant, lactating, or with a positive pregnancy test at screening must be excluded.