This Phase Ia/Ib, open-label, multicenter study will evaluate the safety, tolerability, and preliminary efficacy of DCLL9718S as a single agent (Phase Ia, Arm A) in participants with relapsed or refractory AML or in combination with azacitidine (Phase Ib, Arm B) in participants with previously untreated AML who are not eligible for intensive induction chemotherapy. Each arm will consist of two stages: a dose-escalation stage and an expansion stage. The dose-escalation stage is designed to establish the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) for DCLL9718S alone (Arm A) or in combination with azacitidine (Arm B). The dose-expansion stage is designed to characterize the long-term safety and tolerability of DCLL9718S.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
19
DCLL9718S will be administered as per the schedule specified in the respective arm.
Azacitidine will be administered as per the schedule specified in the respective arm.
City of Hope
Duarte, California, United States
University of Colorado Hospital - Anschutz Cancer Pavilion
Aurora, Colorado, United States
Yale School of Medicine
New Haven, Connecticut, United States
Columbia University Medical Center; Research Pharmacy, Irving Pavillion, Ip 7-749
New York, New York, United States
MD Anderson Cancer Center
Houston, Texas, United States
University of Alberta Hospital
Edmonton, Alberta, Canada
Princess Margaret Hospital; Department of Med Oncology
Toronto, Ontario, Canada
Jewish General Hospital / McGill University
Montreal, Quebec, Canada
Percentage of participants With Adverse Events (AEs)
Time frame: Baseline up to end of study (up to approximately 3 years)
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)
MTD of DCLL9718S
Time frame: Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)
RP2D of DCLL9718S
Time frame: Cycle 1 Day 1 up to Cycle 2 Day 1 (Cycle length: 21 days for Arm A and 28 days for Arm B)
Serum Concentration of DCLL9718S
Time frame: up to 3 years
Plasma Concentration of Azacitidine
Time frame: up to 3 years
Area Under the Concentration-Time Curve (AUC) of DCLL9718S
Time frame: up to 3 years
Maximum Plasma Concentration Observed (Cmax) of DCLL9718S
Time frame: up to 3 years
Total Clearance of DCLL9718S
Time frame: up to 3 years
Terminal Half-Life (t1/2) of DCLL9718S
Time frame: up to 3 years
Volume of Distribution Under Steady-State (Vss) of DCLL9718S
Time frame: up to 3 years
Percentage of Participants With Complete Remission (CR), CR With Incomplete Blood Count Recovery (CRi), CR With Incomplete Platelet Count Recovery (CRp), and Overall Response, Assessed as per International Working Group (IWG) Criteria
Time frame: From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years)
Duration of Response, Assessed as per IWG Criteria
Time frame: From the date of first response to the earliest recurrence or disease progression (up to approximately 3 years)
Overall Survival
Time frame: From the date of first treatment to the date of death from any cause (up to approximately 3 years)
Event-Free Survival (EFS), Assessed as per IWG Criteria
Time frame: From the date of first treatment until treatment failure, relapsed from CR, CRp, or CRi, or death from any cause, whichever occurs first (up to approximately 3 years)
Progression-Free Survival (PFS), Assessed as per IWG Criteria
Time frame: From the date of first treatment to disease progression or relapse or death from any cause (up to approximately 3 years)
Change From Baseline in Anti-Drug Antibody (ADA) to DCLL9718S
Time frame: Baseline up to end of study (up to approximately 3 years)
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