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
- 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
- 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
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.
- 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
- 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
- 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
- Female patients who are pregnant, lactating, or with a positive pregnancy test at
screening must be excluded.