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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Leukemia

Intervention / Treatment
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* Drug: AEG35156


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AEG35156<br>Patient receive AEG35156 prior to chemotherapy | Drug: AEG35156<br>* 2 hr infusion of 650 mg of AEG35156 on days 1, 2, 3 and 8. Idarubicin 12 mg/m2 over 30 minutes daily on each of days 4, 5 and 6. The dose of cytarabine will be 1.5 g/m2 daily by continuous infusion x 4 days (days 4-7) in patients under age 65 and x 3 days (days 4-6) in patients age 65 and above.<br>|
| Sham Comparator: Control<br>Patients receive chemotherapy only | Drug: AEG35156<br>* 2 hr infusion of 650 mg of AEG35156 on days 1, 2, 3 and 8. Idarubicin 12 mg/m2 over 30 minutes daily on each of days 4, 5 and 6. The dose of cytarabine will be 1.5 g/m2 daily by continuous infusion x 4 days (days 4-7) in patients under age 65 and x 3 days (days 4-6) in patients age 65 and above.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine if AEG35156 can enhance the CR and CR with incomplete platelet recovery (CRp) rate and duration of high-dose cytarabine and idarubicin in AML following failure of a single standard dose cytarabine based frontline induction regimen. |  | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine if AEG35156 can enhance overall survival, is safe and measured (Pharmacokinetic) following high-dose cytarabine and idarubicin in AML following failure of a single standard dose cytarabine based frontline induction regimen. |  | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute, myeloid, leukemia, antisense, chemotherapy, idarubicin, cytarabine, Patients with AML, except those with APL (acute promyelocytic leukemia), failing a single standard dose cytarabine based frontline induction regimen.