A Phase 1/1b, Open-label, Dose-escalation, Dose-expansion, Parallel Assignment Study to Evaluate Safety and Clinical Activity of PBCAR0191 (Azercabtagene Zapreleucel or "Azer-cel") in Subjects With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) and r/r B-cell Acute Lymphoblastic Leukemia (B-ALL)
Summary
This is a Phase 1/1b, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study to evaluate the safety and clinical activity of azer-cel, an allogeneic anti-CD19 CAR T, in adults with r/r B ALL, r/r B-cell NHL and CLL/SLL.
Detailed description
This is a multicenter, nonrandomized, open-label, parallel assignment, dose-escalation, and dose-expansion study to evaluate the safety and tolerability, find an appropriate dose to optimize safety and efficacy, and evaluate clinical activity of azer-cel in participants with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL), non-Hodgkin lymphoma (NHL), and chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Before initiating azer-cel, participants will be administered lymphodepletion (LD). At Day 0 of the Treatment Period, participants will receive an intravenous (IV) infusion of azer-cel potentially followed by interleukin-2 (IL-2). All participants will be monitored through D720 or progression. All participants who receive a dose of azer-cel will be asked to consent to a separate long-term follow-up (LTFU) study for up to 15 years after exiting this study.
Arms & interventions
- BiologicalAzer-cel
Infusion of Allogeneic Anti-CD19 CAR T cells
- DrugFludarabine
Specified dose on specified days
- DrugCyclophosphamide
Specified dose on specified days
- DrugIL-2
Specified dose on specified days
Outcome measures
Primary
Phase 1 Dose Escalation/Phase 1b Dose Expansion: Number of Participants with Azer-cel-related AEs Defined as Dose-limiting Toxicities (DLTs)
Time frame: Up to Day 720
Phase 1b Dose Expansion: Objective Response Rate (ORR) B-ALL
ORR for participants with B-ALL will be assessed by National Comprehensive Cancer Network (NCCN) 2017 criteria.
Time frame: Up to Day 720
Phase 1b Dose Expansion: ORR NHL
ORR for participants with NHL will be assessed by Lugano classification, International Workgroup on Chronic Lymphocytic Leukemia (iwCLL) 2018 guidelines, International Primary Central Nervous System Lymphoma Collaborative Group (IPCG) criteria, and International Workshop on Waldenstrom's Macroglobulinemia (IWWM)-11 criteria.
Time frame: Up to Day 720
Secondary
Phase 1 Dose Escalation: ORR
Time frame: Up to Day 720
Complete Response (CR) Rate
Time frame: Up to day 720
Duration of Response (DoR)
Time frame: Up to day 720
Progression-free survival (PFS)
Time frame: Up to day 720
Overall survival (OS)
Time frame: Up to day 720
Time to next treatment (TNT)
Time frame: Up to day 720
Number of Participants with AEs
Time frame: Up to day 720
Eligibility criteria
Study locations (18)
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234
City of Hope
Duarte, California, 91010
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612
Winship Cancer Institute Emory University
Atlanta, Georgia, 30322
Northside Hospital Cancer Institute
Atlanta, Georgia, 30342
University of Maryland
Baltimore, Maryland, 21201
Tufts Medical Center
Boston, Massachusetts, 02111
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215
Barbara Ann Karmanos Cancer Institute (Wayne State University)
Detroit, Michigan, 48201
University of Minnesota
Minneapolis, Minnesota, 55455
Weill Cornell Medical College - NY Presbyterian Hospital
New York, New York, 10021
Columbia University Irving Medical Center/New York Presbyterian Hospital
New York, New York, 10032
Duke University
Durham, North Carolina, 27708
Ohio State University
Columbus, Ohio, 43210
Lifespan Cancer Institute at Rhode Island Hospital
Providence, Rhode Island, 02903
Baylor University Medical Center
Dallas, Texas, 75246
MD Anderson
Houston, Texas, 77030
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226