This is a Phase 1b, open-label, non-randomized, multicenter study to evaluate the safety and pharmacokinetics of orally administered venetoclax (ABT-199) combined with decitabine or azacitidine and the preliminary efficacy of these combinations. In addition, there is a drug-drug interaction (DDI) sub-study only at a single site, to assess the pharmacokinetics and safety of venetoclax (ABT-199) in combination with posaconazole.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
212
Posaconazole will be administered orally twice a day on Cycle 1 Day 21 and once daily from Cycle 1 Day 22 to Cycle 1 Day 28.
ABT-199 is taken orally once daily starting on Day 2 of cycle 1 and begin on day 1 of every other cycle thereafter. This is a dose escalation study, therefore the dose of ABT-199 will change.
Decitabine will be administered by IV infusion over 1 hour beginning on Day 1 thru Day 5 of each Cycle for a minimum of 4 Cycles
Azacitidine will be administered by IV infusion over 10 to 40 minutes or subcutaneously based on the institutional guidelines, beginning on Day 1 through Day 7 of each Cycle, for a minimum of 4 Cycles.
City of Hope /ID# 129718
Duarte, California, United States
University of California, Davis Comprehensive Cancer Center /ID# 129719
Sacramento, California, United States
Univ of Colorado Cancer Center /ID# 127859
Aurora, Colorado, United States
Emory Midtown Infectious Disease Clinic /ID# 129715
Atlanta, Georgia, United States
Northwestern University Feinberg School of Medicine /ID# 128741
Chicago, Illinois, United States
The University of Chicago Medical Center /ID# 128742
Chicago, Illinois, United States
Johns Hopkins University /ID# 129699
Baltimore, Maryland, United States
Dana-Farber Cancer Institute /ID# 127857
Boston, Massachusetts, United States
Columbia University Medical Center /ID# 130289
New York, New York, United States
Duke Cancer Center /ID# 129720
Durham, North Carolina, United States
...and 13 more locations
Number of Participants Experiencing Adverse Events (AEs)
An adverse event (AE) is defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment. The investigator assesses the relationship of each event to the use of study drug.
Time frame: Measured up to 1 year after the last subject last dose
Maximum observed plasma concentration (Cmax)
Maximum observed concentration, occurring at Tmax.
Time frame: For approximately 5 days following a single dose of ABT-199.
Time to Cmax (peak time, Tmax),
The time at which maximum plasma concentration (Cmax) is observed.
Time frame: For approximately 5 days following a single dose of ABT-199.
The area under the plasma concentration-time curve (AUC) from 0 to 24 hours (AUC0-24)
The area under the plasma concentration-time curve (AUC) over a 24-hour dose interval.
Time frame: For approximately 5 days following a single dose of ABT-199.
Half-Life (t1/2)
The time required for the concentration of the drug to reach half of its original value.
Time frame: For approximately 5 days following a single dose of ABT-199.
Clearance (CL)
Clearance is defined as the rate at which drug is cleared from the blood.
Time frame: For approximately 5 days following a single dose of ABT-199.
Complete Remission Rate
Complete Remission Rate will be determined by the number of subjects who achieve a Complete Remission.
Time frame: Measured up to 1 year after the last subject last dose
Complete Remission with incomplete blood count recovery rate
Complete Remission with incomplete blood count recovery rate will be determined by the number of subjects who achieve a Complete Remission with incomplete blood count recovery.
Time frame: Measured up to 1 year after the last subject last dose
Overall Response Rate
Overall response rate will be defined as the proportion of subjects who achieve a complete remission (CR), complete remission incomplete (CRi), or partial remission (PR) per the International Working Group criteria for AML.
Time frame: Measured up to 1 year after the last subject last dose
Overall Survival
Overall survival will be defined as the number of days from the date of first dose to the date of death.
Time frame: Measured up to 1 year after the last subject last dose
Event Free Survival
Event-free survival (EFS) will be defined as the number of days from the date of first dose to the date of earliest evidence of relapse, subsequent treatment other than stem cell transplant while in composite complete response (CR + CRi), or death.
Time frame: Measured up to 1 year after the last subject last dose
Duration of Response
Duration of response will be defined as the number of days from the date of first response per the IWG criteria for AML to the earliest recurrence or progressive disease (PD).
Time frame: Measured up to 1 year after the last subject last dose
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