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.
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).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
54
2 days loading dose followed by weekly 2hr infusion
Norris Cancer Center - University of Southern California
Los Angeles, California, United States
UCLA Medical Center
Los Angeles, California, United States
Northwestern Memorial Hospital
Chicago, Illinois, United States
Johns Hopkins - Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
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
Effects of AEG35156 on XIAP mRNA and protein expression and plasma pharmacokinetic profile of AEG35156.
Time frame: 1 year
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M.D. Anderson Cancer Center
Houston, Texas, United States
Princess Margaret Hospital
Toronto, Ontario, Canada
Hopital Maisonneuve-Rosemont
Montreal, Quebec, Canada