Dose-escalation and Dose-expansion Study of Safety of Azer-cel (PBCAR0191) in Participants With Relapsed/Refractory (r/r) Non-Hodgkin Lymphoma (NHL) and r/r B-cell Acute Lymphoblastic Leukemia (B-ALL)
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)
1 other identifier
interventional
135
2 countries
23
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Mar 2019
Longer than P75 for phase_1
23 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 20, 2018
CompletedFirst Posted
Study publicly available on registry
September 11, 2018
CompletedStudy Start
First participant enrolled
March 11, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2027
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2027
February 2, 2026
January 1, 2026
8.2 years
August 20, 2018
January 28, 2026
Conditions
Outcome Measures
Primary Outcomes (3)
Phase 1 Dose Escalation/Phase 1b Dose Expansion: Number of Participants with Azer-cel-related AEs Defined as Dose-limiting Toxicities (DLTs)
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.
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.
Up to Day 720
Secondary Outcomes (7)
Phase 1 Dose Escalation: ORR
Up to Day 720
Complete Response (CR) Rate
Up to day 720
Duration of Response (DoR)
Up to day 720
Progression-free survival (PFS)
Up to day 720
Overall survival (OS)
Up to day 720
- +2 more secondary outcomes
Study Arms (6)
Phase 1 Dose Escalation: Azer-cel Dose Level 1
EXPERIMENTALAzer-cel, 3 x 10\^5 CAR T cells per kilogram (kg) body weight. Route of Administration: Intravenous infusion
Phase 1 Dose Escalation: Azer-cel Dose Level 2
EXPERIMENTALAzer-cel, 1 x 10\^6 CAR T cells per kg body weight. Route of Administration: Intravenous infusion
Phase 1 Dose Escalation: Azer-cel Dose Level 3a
EXPERIMENTALAzer-cel, 3 x 10\^6 CAR T cells per kg body weight. Route of Administration: Intravenous infusion
Phase 1 Dose Escalation: Azer-cel Dose Level 4
EXPERIMENTALAzer-cel, 6 x 10\^6 CAR T cells per kg body weight as 2 administrations of 3 x 10\^6 CAR T cells per kg body weight on Day 0 and Day 10. Route of Administration: Intravenous infusion
Phase 1 Dose Escalation: Azer-cel Dose Level 4b
EXPERIMENTALAzer-cel, 500 x 10\^6 CAR T cells (flat dose). Route of Administration: Intravenous infusion
Phase 1B Dose Expansion: Azer-cel
EXPERIMENTALAzer-cel will be administered at a dose level established in Phase 1. Route of Administration: Intravenous infusion
Interventions
Infusion of Allogeneic Anti-CD19 CAR T cells
Specified dose on specified days
Specified dose on specified days
Eligibility Criteria
You may qualify if:
- Criteria for B-ALL:
- Participant has confirmed unequivocal r/r CD19+ B-ALL.
- Criteria for NHL and CLL/SLL:
- Participant has unequivocal aggressive CD19+ r/r B-cell NHL that is confirmed by tumor biopsy tissue from last relapse after CD19-directed therapy.
- For Phase 1 Dose Escalation:
- Diffuse large B-cell lymphoma (DLBCL) including Richter's transformation
- Follicular lymphoma (FL) including Grade 3 or transformed FL
- High-grade B-cell lymphoma (HGBCL)
- Primary mediastinal lymphoma
- For Phase 1b Dose Expansion (CAR T-relapsed cohort):
- DLBCL not otherwise specified (NOS)
- HGBCL
- DLBCL transformed from the following indolent lymphoma subtypes (FL, Marginal Zone lymphoma \[MZL\], and Waldenstrom's Macroglobulinemia \[WM\])
- Other large B-cell lymphoma (LBCL) subtypes may be enrolled with approval from the Medical Monitor.
- Participants previously treated with CD19-directed autologous CAR T therapies have received no more than 2 lines of therapy after administration of their previous CAR T product.
- +16 more criteria
You may not qualify if:
- Criteria for B-ALL:
- Burkitt cell (L3 ALL) or mixed-lineage acute leukemia.
- Criteria for NHL:
- Requirement for urgent therapy due to tumor mass effects such as bowel obstruction or blood vessel compression.
- Active hemolytic anemia.
- Criteria for B-ALL and NHL:
- No active CNS disease, excluding PCNSL
- History of another primary malignancy
- Any form of primary immunodeficiency (for example, severe combined immunodeficiency disease).
- History of hepatitis B or hepatitis C currently receiving ongoing antiviral therapy.
- Any known uncontrolled cardiovascular disease at the time of Screening that, in the investigator's opinion, renders the participant ineligible
- History of hypertension crisis or hypertensive encephalopathy within 3 months prior to Screening.
- History of severe immediate hypersensitivity reaction to any of the agents used in this study.
- Presence of a CNS disorder that, in the opinion of the investigator, renders the participant ineligible for treatment.
- History of concomitant genetic syndrome such as Fanconi anemia, Kostmann syndrome, Shwachman-Diamond syndrome, or any other known bone marrow failure syndrome.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Imugene Limitedlead
Study Sites (23)
Banner MD Anderson Cancer Center
Gilbert, Arizona, 85234, United States
City of Hope
Duarte, California, 91010, United States
H. Lee Moffitt Cancer Center
Tampa, Florida, 33612, United States
Winship Cancer Institute Emory University
Atlanta, Georgia, 30322, United States
Northside Hospital Cancer Institute
Atlanta, Georgia, 30342, United States
University of Maryland
Baltimore, Maryland, 21201, United States
Tufts Medical Center
Boston, Massachusetts, 02111, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, 02215, United States
Barbara Ann Karmanos Cancer Institute (Wayne State University)
Detroit, Michigan, 48201, United States
University of Minnesota
Minneapolis, Minnesota, 55455, United States
Weill Cornell Medical College - NY Presbyterian Hospital
New York, New York, 10021, United States
Columbia University Irving Medical Center/New York Presbyterian Hospital
New York, New York, 10032, United States
Duke University
Durham, North Carolina, 27708, United States
Ohio State University
Columbus, Ohio, 43210, United States
Lifespan Cancer Institute at Rhode Island Hospital
Providence, Rhode Island, 02903, United States
Baylor University Medical Center
Dallas, Texas, 75246, United States
MD Anderson
Houston, Texas, 77030, United States
Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Royal Prince Alfred Hospital
Camperdown, New South Wales, 2050, Australia
Liverpool Hospital
Liverpool, New South Wales, 2170, Australia
Royal Adelaide Hospital
Adelaide, South Australia, 5000, Australia
St Vincent's Hospital Melbourne
Fitzroy, Victoria, 3065, Australia
Barwon Health - Andrew Love Cancer Centre
Geelong, Victoria, 3320, Australia
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- STUDY CHAIR
John Byon, MD, PhD
Imugene Limited
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
August 20, 2018
First Posted
September 11, 2018
Study Start
March 11, 2019
Primary Completion (Estimated)
June 1, 2027
Study Completion (Estimated)
June 1, 2027
Last Updated
February 2, 2026
Record last verified: 2026-01
Data Sharing
- IPD Sharing
- Will not share