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

Sponsor

Aegera Therapeutics (Industry)

Overall Status

Terminated

CT.gov ID

NCT01018069

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

3.3

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: AEG35156	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Nov 1, 2009

Actual Primary Completion Date :

Oct 1, 2010

Actual Study Completion Date :

Oct 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: AEG35156 Patient receive AEG35156 prior to chemotherapy	Drug: AEG35156 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.
Sham Comparator: Control Patients receive chemotherapy only	Drug: AEG35156 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.

Arm

Intervention/Treatment

Active Comparator: AEG35156

Patient receive AEG35156 prior to chemotherapy

Drug: AEG35156

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.

Sham Comparator: Control

Patients receive chemotherapy only

Drug: AEG35156

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UCLA School of Medicine	Los Angeles	California	United States	90095
2	Rocky Mountain Blood & Marrow Transplant Program	Denver	Colorado	United States	80218
3	Northwestern University Med School, div. Oncology & Hematology	Chicago	Illinois	United States	60611
4	New York Medical College	Valhalla	New York	United States	10595
5	MD Anderson Cancer Center University of Texas	Houston	Texas	United States	77303
6	Cancer Research Institute of Scott & White Hospital	Temple	Texas	United States	76502
7	Princess Margaret Hospital	Toronto	Ontario	Canada
8	Hopital Charles Lemoyne	Greenfield Park	Quebec	Canada	J4V 2H1
9	Hopital Maisonneuve-Rosemont	Montreal	Quebec	Canada
10	Hopital Sacre Coeur	Montreal	Quebec	Canada
11	Klinikum Chemnitz gGmbH	Chemnitz		Germany	09113
12	St. Johannes Hospital	Duisburg		Germany	47166
13	Universitatsklinimum Essen	Essen		Germany	45147
14	Universitatsklinikum Hamburg-Eppendorf	Hamburg		Germany	20246
15	2. Medizinische Klinik und Poliklinik im Stadtischen Krankenhaus Kile GmgH	Kiel		Germany	24116
16	III. Medizinische Klinik und Poliklinik der Johannes Gutenberg-Universitat	Mainz		Germany	55131
17	Medizinische Klinik a Hamatologie und Onkologie	Munster		Germany	48129
18	Robert Boasch Krankenhaus Stuttgart	Stuttgart		Germany	70376