Clinical trial NCT01018069: AEG35156 in Combination With High-dose Cytarabine and Idarubicin in AML Following Failure of a Single Standard Dose Cytarabine Based Frontline Induction Regimen
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 type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Leukemia
Keywords: 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.
Lead sponsor: Aegera Therapeutics
Sponsor class: INDUSTRY
First posted: 2009-11-23
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: 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.
timeFrame: 1 year
Secondary outcomes:
measure: 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.
timeFrame: 1 year
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA School of Medicine
state: California
city: Denver
country: United States
facility: Rocky Mountain Blood & Marrow Transplant Program
state: Colorado
city: Chicago
country: United States
facility: Northwestern University Med School, div. Oncology & Hematology
state: Illinois
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Houston
country: United States
facility: MD Anderson Cancer Center University of Texas
state: Texas
city: Temple
country: United States
facility: Cancer Research Institute of Scott & White Hospital
state: Texas
city: Toronto
country: Canada
facility: Princess Margaret Hospital
state: Ontario
city: Greenfield Park
country: Canada
facility: Hopital Charles Lemoyne
state: Quebec
city: Montreal
country: Canada
facility: Hopital Maisonneuve-Rosemont
state: Quebec
city: Montreal
country: Canada
facility: Hopital Sacre Coeur
state: Quebec
city: Chemnitz
country: Germany
facility: Klinikum Chemnitz gGmbH
city: Duisburg
country: Germany
facility: St. Johannes Hospital
city: Essen
country: Germany
facility: Universitatsklinimum Essen
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf
city: Kiel
country: Germany
facility: 2. Medizinische Klinik und Poliklinik im Stadtischen Krankenhaus Kile GmgH
city: Mainz
country: Germany
facility: III. Medizinische Klinik und Poliklinik der Johannes Gutenberg-Universitat
city: Munster
country: Germany
facility: Medizinische Klinik a Hamatologie und Onkologie
city: Stuttgart
country: Germany
facility: Robert Boasch Krankenhaus Stuttgart
Study officials:
affiliation: Princess Margaret Hospital, Canada
name: Aaron Schimmer, MD
role: PRINCIPAL_INVESTIGATOR
References: