This is a non-randomized, open-label, Phase Ib study of atezolizumab in combination with immunomodulatory agents for the treatment of participants with AML (relapsed/refractory and treatment-naive, elderly participants unfit for induction chemotherapy). The study has been designed with the intent, over time, to study multiple combinations of atezolizumab with different immunomodulatory agents in participants with AML. The study will begin with the evaluation of the combination of atezolizumab and guadecitabine (Arm A). In the future, additional arms may be added.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Atezolizumab 840 mg administered by IV infusion on Days 8 and 22 of each 28-day cycle.
Guadecitabine 60 mg/m\^2 SC on Days 1-5 of every 28-day cycle.
City of Hope
Duarte, California, United States
Yale University
New Haven, Connecticut, United States
The NewYork-Presbyterian Hospital Columbia University Medical Center
New York, New York, United States
Memorial Sloan Kettering Cancer Center
New York, New York, United States
Levine Cancer Institute
Charlotte, North Carolina, United States
Temple University Hospital
Philadelphia, Pennsylvania, United States
Huntsman Cancer Institute
Salt Lake City, Utah, United States
The University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin, United States
Percentage of Participants with Adverse Events
Time frame: Baseline up to approximately 32 months
Percentage of Participants with Complete Remission (CR) as Defined by International Working Group (IWG) 2003 and European Leukemia Net (ELN) 2010 Response Criteria
Time frame: After 6 cycles of combination therapy (at Week 24; each cycle is 28 days)
Percentage of Participants with Complete Remission with Incomplete Platelet Recovery (CRp) as Defined by IWG 2003 and ELN 2010 Response Criteria
Time frame: After 6 cycles of combination therapy (at Week 24; each cycle is 28 days)
Percentage of Participants with Complete Remission with Incomplete Recovery (CRi) as Defined by IWG 2003 and ELN 2010 Response Criteria
Time frame: After 6 cycles of combination therapy (at Week 24; each cycle is 28 days)
Duration of Response as Defined by IWG 2003 and ELN 2010 Response Criteria
Time frame: Baseline until the date of relapse/progression or death from any cause, assessed up to approximately 32 months
Percentage of Participants with Best Overall Response as Defined by IWG 2003 and ELN 2010 Response Criteria
Time frame: Baseline until the date of relapse/progression or death from any cause, assessed up to approximately 32 months
Event-free Survival (EFS) as Defined by IWG 2003 and ELN 2010 Response Criteria
Time frame: Baseline until the date of induction treatment failure or relapse or death from any cause, assessed up to approximately 32 months
Leukemia-free Survival (LFS) as Defined by IWG 2003 and ELN 2010 Response Criteria
Time frame: Baseline until the date of relapse or death from any cause, assessed up to approximately 32 months
Overall Survival (OS)
Time frame: Baseline until death from any cause, assessed up to approximately 32 months
Percentage of Participants with Minimal Residual Disease (MRD) Negativity in Participants who Achieve CR, CRp, or CRi
Time frame: Baseline up to approximately 32 months
Percentage of Participants with Anti-Drug Antibody (ADA) to Atezolizumab
Time frame: Pre-infusion (0 hours [hrs]) on Day (D) 1 of Cycle (C) 1; D8 of C2, C3, C4, C6, and every 6 cycles thereafter until treatment discontinuation (up to 32 months); at 120 days and 1 year after atezolizumab last dose (up to 32 months; each cycle is 28 days)
Serum Concentration of Atezolizumab
Pre-infusion (0 hrs) on D1 of C1, C4; 30 minutes after end of infusion (infusion duration=30-60 minutes) on D8 of C1, C2, C4; Pre infusion (0 hrs) on D22 of C1, D8 of C2, C3, C4, C6, every 6 cycles thereafter until treatment discontinuation (up to 32 months); at 120 days and 1 year after atezolizumab last dose (up to 32 months; each cycle is 28 days)
Time frame: Day 1 up to 32 months (detailed sample collection time points are provided in Outcome Measure Description)
Plasma Concentration of Guadecitabine
Time frame: 1, 2, 5, and 8 hours post-injection on D1 of C1 and C4, 1 hour post-injection on D1 of C2, C3, C6, and every 6 cycles thereafter (up to 32 months; each cycle is 28 days)
Plasma Concentration of Decitabine (a Metabolite Product of Guadecitabine)
Time frame: 1, 2, 5, and 8 hours post-injection on D1 of C1 and C4, 1 hour post-injection on D1 of C2, C3, C6, and every 6 cycles thereafter (up to 32 months; each cycle is 28 days)
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