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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01018069
• Other study ID #: AEG35156-206
• Secondary ID: 2009-013669-25
• Status: Terminated
• Phase: Phase 2
• First received: November 19, 2009
• Last updated: July 12, 2011
• Start date: November 2009
• Est. completion date: October 2010

Study information

• Verified date: July 2011
• Source: Aegera Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health CanadaGermany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 60
• Est. completion date: October 2010
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Leukemia

Intervention

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.

Locations

Country	Name	City	State
Canada	Hopital Charles Lemoyne	Greenfield Park	Quebec
Canada	Hopital Maisonneuve-Rosemont	Montreal	Quebec
Canada	Hopital Sacre Coeur	Montreal	Quebec
Canada	Princess Margaret Hospital	Toronto	Ontario
Germany	Klinikum Chemnitz gGmbH	Chemnitz
Germany	St. Johannes Hospital	Duisburg
Germany	Universitatsklinimum Essen	Essen
Germany	Universitatsklinikum Hamburg-Eppendorf	Hamburg
Germany	2. Medizinische Klinik und Poliklinik im Stadtischen Krankenhaus Kile GmgH	Kiel
Germany	III. Medizinische Klinik und Poliklinik der Johannes Gutenberg-Universitat	Mainz
Germany	Medizinische Klinik a Hamatologie und Onkologie	Munster
Germany	Robert Boasch Krankenhaus Stuttgart	Stuttgart
United States	Northwestern University Med School, div. Oncology & Hematology	Chicago	Illinois
United States	Rocky Mountain Blood & Marrow Transplant Program	Denver	Colorado
United States	MD Anderson Cancer Center University of Texas	Houston	Texas
United States	UCLA School of Medicine	Los Angeles	California
United States	Cancer Research Institute of Scott & White Hospital	Temple	Texas
United States	New York Medical College	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
Aegera Therapeutics

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes