Study of XIAP Antisense Given With Chemotherapy for Refractory/Relapsed AML

This study has been completed.
Sponsor:
Information provided by:
Aegera Therapeutics
ClinicalTrials.gov Identifier:
NCT00363974
First received: August 10, 2006
Last updated: November 30, 2009
Last verified: November 2009
  Purpose

The purpose of this study is to determine if the drug, called AEG35156, can be safely given to AML patients and whether it effectively reduces levels of a protein (XIAP) to increase the sensitivity of cancer cells to chemotherapy (ara-C and idarubicin) in patients with refractory or relapsed AML.


Condition Intervention Phase
Leukemia, Myelomonocytic, Acute
Drug: XIAP antisense
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Phase I/II Study of XIAP Antisense AEG35156 Administered to Patients With Refractory/Relapsed AML in Combination With Chemotherapy

Resource links provided by NLM:


Further study details as provided by Aegera Therapeutics:

Primary Outcome Measures:
  • Dose at which AEG35156 when combined with fixed doses of ara-C and idarubicin, produces acceptable CR and toxicity rates as defined and observed at 30 days post-last dose [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Effects of AEG35156 on XIAP mRNA and protein expression and plasma pharmacokinetic profile of AEG35156. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 54
Study Start Date: October 2005
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: XIAP antisense
    2 days loading dose followed by weekly 2hr infusion
Detailed Description:

This is a phase I/II, single-arm, open-label, study to establish the recommended dose and activity of AEG35156 administered as a daily x3 two-hour infusion prior to reinduction chemotherapy with idarubicin and ara-C followed by weekly two-hour AEG35156 infusions. Subjects eligible for study entry must have confirmed diagnosis of AML in first relapse after an initial CR that lasted less than 6 months or primary refractory AML. Fixed dose of idarubicin and ara-C will be given, plus one of eight doses of AEG35156: 12, 24, 48, 75, 110, 165, 250 and 350mg/m2. A maximum of 54 patients will be treated in cohorts of size 3, starting at 12mg/m2, and not skipping any untried dose level when escalating. Following dose escalation, approximately 20 patients will be treated at the best acceptable dose as determined by the method of Thall and Cook (2004).

  Eligibility

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

Inclusion Criteria

  • Subjects with relapsed or refractory AML, except those with APL (acute promyelocytic leukemia), that are about to receive their initial treatment for first relapse after an initial CR that lasted less than 6 months or for primary refractory AML that have an expected complete response rate ≤20%. The initial diagnosis of AML has to be based on the presence of > 10% blasts in marrow or blood, and the diagnosis of relapsed/refractory AML 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 < 100,000 /uL, or neutrophil count < 1000 /uL).
  • Peripheral AML blast count < 50,000 /uL that is not projected to rise above 50,000 /uL within 5 days of beginning treatment.
  • Subjects must have an Eastern Cooperative Oncology Group (ECOG) performance status of ≤2.
  • Subjects must be >18 years old.
  • Male, or female subjects who are post-menopausal (amenorrhagic for at least 12 months), or surgically or biologically sterile. Females of childbearing potential with a negative serum pregnancy test 72-96 hours prior to the 1st infusion in the study and using adequate forms of contraception for the duration of the study, including 30 days after the last treatment. Adequate methods of contraception should be used by both male and female subjects.
  • Subjects must have adequate organ and immune function as indicated by the following laboratory values:

    • Parameter Laboratory Values
    • Serum creatinine; <2.0mg/dL
    • Total Bilirubin <2.0mg/dL
    • AST (SGOT) and ALT (SGPT) <3 X ULN * *ULN: Institution's upper limit of normal.
  • The subject must understand and be able and willing and likely to fully comply with study procedures, including scheduled follow-up, and restrictions.
  • The subject, or the subject's legal guardian, must have given written personally signed and dated informed consent to participate in the study, in accordance with the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) Guidelines, before completing any study related procedures.

Exclusion Criteria

  • Clinical evidence of active CNS leukemic involvement.
  • Patients with left-ventricular ejection fractions <50%.
  • Active and uncontrolled infection. Patients with an infection that 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 subject'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 materials [or closely related compounds] or any of their stated ingredients.
  • History of alcohol or other substance abuse within the last year.
  • Use of another investigational agent or participation in a clinical trial within the last 14 days prior to enrolment. Subjects who have used a previous AS agent for at least 90 days will be excluded.
  • Female subjects who are pregnant or lactating, or females with a positive pregnancy test at screening must be excluded.
  • Subjects that have previously been enrolled into this study and subsequently withdrawn must also 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: NCT00363974

Locations
United States, California
UCLA Medical Center
Los Angeles, California, United States, 90095
Norris Cancer Center - University of Southern California
Los Angeles, California, United States, 90033
United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
United States, Maryland
Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States, 21231
United States, Texas
M.D. Anderson Cancer Center
Houston, Texas, United States, 77030-4009
Canada, Ontario
Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Hopital Maisonneuve-Rosemont
Montreal, Quebec, Canada
Sponsors and Collaborators
Aegera Therapeutics
Investigators
Study Director: Jacques Jolivet, MD Aegera Therapeutics Inc.
  More Information

Publications:
Responsible Party: Jacques Jolivet, MD, Senior VP Clinical, Aegera Therapeutics Inc
ClinicalTrials.gov Identifier: NCT00363974     History of Changes
Other Study ID Numbers: AEG35156-103, MDA 2005-0384, PMH 05-0452-C
Study First Received: August 10, 2006
Last Updated: November 30, 2009
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Aegera Therapeutics:
AML
leukemia
relapse
refractory
antisense
oligonucleotide

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelomonocytic, Acute
Neoplasms by Histologic Type
Neoplasms
Leukemia, Myeloid

ClinicalTrials.gov processed this record on August 18, 2014