The primary objective for this study is to assess the safety and tolerability as well as preliminary efficacy of venetoclax in combination with cobimetinib, and venetoclax in combination with idasanutlin in patients with relapsed or refractory acute myeloid leukemia (R/R) AML who are not eligible for cytotoxic therapy.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
88
Cobimetinib will be administered orally as per schedule in Arm description.
Idasanutlin will be administered orally as per schedule in Arm description.
Venetoclax will be administered orally as per schedule in Arm description.
USC Norris Cancer Center
Los Angeles, California, United States
UC Davis; Comprehensive Cancer Center
Sacramento, California, United States
Number of Participants with Dose Limiting Toxicities (DLTs)
Time frame: From Cycle 1 Day 1 to Cycle 2 Day 1 for a minimum of 28 days
Number of Participants with Adverse Events (AEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)
Time frame: Baseline up until 30 days after the last dose of study drug (up to a maximum of 4 years, 9 months)
Overall Response Rate (ORR) (Complete Remission (CR) + Complete Remission with Incomplete Blood Recovery (CRi) + Incomplete Platelet Count Recovery (CRp) + Partial Remission/Partial Response [PR])
Time frame: Up to 2 years
Complete Remission/complete response (CR) + Complete Remission with Incomplete Blood Recovery (CRi) + Incomplete Platelet Count Recovery (CRp)
Time frame: Up to 2 years
CR + Complete Remission with Partial Hematologic Recovery (CRh) Rate
Time frame: Up to 2 years
Duration of Response (DOR)
Time frame: Up to 2 years
Time to Progression (TTP)
Time frame: Up to 2 years
Progression-Free Survival (PFS)
Time frame: Up to 2 years
Event-Free Survival (EFS)
Time frame: Up to 2 years
Leukemia-Free Survival (LFS)
Time frame: Up to 2 years
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Univ of Calif, San Francisco
San Francisco, California, United States
University of Colorado
Aurora, Colorado, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
Weill Cornell Medical College
New York, New York, United States
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, United States
MD Anderson Cancer Center
Houston, Texas, United States
University of Alberta Hospital
Edmonton, Alberta, Canada
Princess Margaret Cancer Center
Toronto, Ontario, Canada
...and 7 more locations
Overall Survival (OS)
Time frame: Up to 2 years
Pharmacokinetics of Venetoclax Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-24hr)
Time frame: Up to 6 months
Pharmacokinetics of Venetoclax Maximum Observed Concentration (Cmax)
Time frame: Up to 6 months
Pharmacokinetics of Cobimetinib Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-24hr)
Time frame: Up to 6 months
Pharmacokinetics of Cobimetinib Maximum Observed Concentration (Cmax)
Time frame: Up to 6 months
Pharmacokinetics of Idasanutlin Area Under the Concentration-Time Curve from Time Zero to Last Measurable Concentration (AUC0-24hr)
Time frame: Up to 6 months
Pharmacokinetics of Idasanutlin Maximum Observed Concentration (Cmax)
Time frame: Up to 6 months
Number of Participants Reporting Symptoms in Patient-Reported Outcomes of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) Questionnaire
Time frame: Up to 2 years
Rate of Transfusion Independence
Time frame: Up to 2 years
Duration Of Transfusion Independence, Defined As The Number Of Consecutive Days Of Transfusion Independence, Measured From 1 Day After Last Transfusion To Disease Progression Or Subsequent Transfusion
Time frame: Up to 2 years
Minimal Residual Disease (MRD) In The Bone Marrow To Evaluate The Depth Of Response
Time frame: Up to 2 years