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

This study has been terminated.
(Failed to reach endpoints)
Sponsor:
Information provided by:
Aegera Therapeutics
ClinicalTrials.gov Identifier:
NCT01018069
First received: November 19, 2009
Last updated: July 12, 2011
Last verified: July 2011
  Purpose

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 Intervention Phase
Leukemia
Drug: AEG35156
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Aegera Therapeutics:

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. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

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. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 60
Study Start Date: November 2009
Study Completion Date: October 2010
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01018069

Locations
United States, California
UCLA School of Medicine
Los Angeles, California, United States, 90095
United States, Colorado
Rocky Mountain Blood & Marrow Transplant Program
Denver, Colorado, United States, 80218
United States, Illinois
Northwestern University Med School, div. Oncology & Hematology
Chicago, Illinois, United States, 60611
United States, New York
New York Medical College
Valhalla, New York, United States, 10595
United States, Texas
MD Anderson Cancer Center University of Texas
Houston, Texas, United States, 77303
Cancer Research Institute of Scott & White Hospital
Temple, Texas, United States, 76502
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada
Canada, Quebec
Hopital Charles Lemoyne
Greenfield Park, Quebec, Canada, J4V 2H1
Hopital Sacre Coeur
Montreal, Quebec, Canada
Hopital Maisonneuve-Rosemont
Montreal, Quebec, Canada
Germany
Klinikum Chemnitz gGmbH
Chemnitz, Germany, 09113
St. Johannes Hospital
Duisburg, Germany, 47166
Universitatsklinimum Essen
Essen, Germany, 45147
Universitatsklinikum Hamburg-Eppendorf
Hamburg, Germany, 20246
2. Medizinische Klinik und Poliklinik im Stadtischen Krankenhaus Kile GmgH
Kiel, Germany, 24116
III. Medizinische Klinik und Poliklinik der Johannes Gutenberg-Universitat
Mainz, Germany, 55131
Medizinische Klinik a Hamatologie und Onkologie
Munster, Germany, 48129
Robert Boasch Krankenhaus Stuttgart
Stuttgart, Germany, 70376
Sponsors and Collaborators
Aegera Therapeutics
Investigators
Principal Investigator: Aaron Schimmer, MD Princess Margaret Hospital, Canada
  More Information

No publications provided

Responsible Party: Jacques Jolivet, Aegera Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT01018069     History of Changes
Other Study ID Numbers: AEG35156-206, 2009-013669-25
Study First Received: November 19, 2009
Last Updated: July 12, 2011
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Aegera Therapeutics:
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.

Additional relevant MeSH terms:
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Idarubicin
X-Linked Inhibitor of Apoptosis Protein
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Caspase Inhibitors
Cysteine Proteinase Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on August 28, 2014