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)

January 28, 2026 updated by: Imugene Limited

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)

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

135

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Imugene Clinical Team
  • Phone Number: +1 984 245 0082
  • Email: info@imugene.com

Study Contact Backup

  • Name: Imugene Clinical Team
  • Phone Number: +61 2 9423 0881
  • Email: info@imugene.com

Study Locations

  • Australia
    • New South Wales
      • Camperdown, New South Wales, Australia, 2050
        • Recruiting
        • Royal Prince Alfred Hospital
        • Contact:
          • Dr Vinay Vanguru
      • Liverpool, New South Wales, Australia, 2170
        • Recruiting
        • Liverpool Hospital
        • Contact:
          • Dr Nagendra P Sungala
    • South Australia
      • Adelaide, South Australia, Australia, 5000
        • Recruiting
        • Royal Adelaide Hospital
        • Contact:
          • Dr Danielle Blunt
    • Victoria
      • Fitzroy, Victoria, Australia, 3065
        • Recruiting
        • St Vincent's Hospital Melbourne
        • Principal Investigator:
          • Matthew Ku
      • Geelong, Victoria, Australia, 3320
        • Recruiting
        • Barwon Health - Andrew Love Cancer Centre
        • Principal Investigator:
          • Hannah Rose
  • United States
    • Arizona
      • Gilbert, Arizona, United States, 85234
        • Completed
        • Banner MD Anderson Cancer Center
    • California
      • Duarte, California, United States, 91010
        • Completed
        • City of Hope
    • Florida
      • Tampa, Florida, United States, 33612
        • Recruiting
        • H. Lee Moffitt Cancer Center
        • Principal Investigator:
          • Bijal Shah, MD
        • Contact:
          • Clinical Research
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Winship Cancer Institute Emory University
        • Contact:
          • Clinical Trials
        • Principal Investigator:
          • Edmund Waller, MD
      • Atlanta, Georgia, United States, 30342
        • Recruiting
        • Northside Hospital Cancer Institute
        • Contact:
          • Clinical Trials
        • Principal Investigator:
          • Scott Solomon, MD
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Recruiting
        • University of Maryland
        • Contact:
          • Clinical Trials
        • Principal Investigator:
          • Jean Yared, MD
    • Massachusetts
      • Boston, Massachusetts, United States, 02111
        • Recruiting
        • Tufts Medical Center
        • Contact:
          • Clinical Trials
        • Principal Investigator:
          • Andreas Klein, MD
      • Boston, Massachusetts, United States, 02215
        • Completed
        • Dana-Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Completed
        • Barbara Ann Karmanos Cancer Institute (Wayne State University)
    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Recruiting
        • University of Minnesota
        • Contact:
          • Clinical Research
        • Principal Investigator:
          • Supriya Gupta, MD
    • New York
      • New York, New York, United States, 10032
        • Recruiting
        • Columbia University Irving Medical Center/New York Presbyterian Hospital
        • Contact:
          • Clinical Trials
        • Principal Investigator:
          • Ran Reshef, MD
      • New York, New York, United States, 10021
        • Completed
        • Weill Cornell Medical College - NY Presbyterian Hospital
    • North Carolina
      • Durham, North Carolina, United States, 27708
        • Completed
        • Duke University
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Completed
        • Ohio State University
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Recruiting
        • Lifespan Cancer Institute at Rhode Island Hospital
        • Contact:
          • Clinical Trials
        • Principal Investigator:
          • Adam Olszewski, MD
    • Texas
      • Dallas, Texas, United States, 75246
        • Recruiting
        • Baylor University Medical Center
        • Contact:
          • Clinical Trials
        • Principal Investigator:
          • Houston Holmes III, MD
      • Houston, Texas, United States, 77030
        • Completed
        • MD Anderson
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Recruiting
        • Medical College of Wisconsin
        • Principal Investigator:
          • Nirav Shah, MD
        • Contact:
          • Clinical Trials

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Key Inclusion Criteria

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.
  • For the expansion CAR T-relapsed cohort only: Participants must have received autologous CD19-directed CAR T therapy and demonstrated clinical response to the treatment at Day 28 or later, followed by relapse or progression.

For Phase 1b dose expansion (CAR T-naive cohort):

  • DLBCL NOS
  • DLBCL transformed from the following indolent lymphoma subtypes (FL, MZL, and WM)
  • HGBCL
  • FL (Grade 1-3a)
  • MZL that is fluorodeoxyglucose (FDG)-avid on positron emission tomography (PET) scan
  • WM
  • CLL/SLL
  • Primary central nervous system (CNS) lymphoma (PCNSL)
  • Other LBCL subtypes may be enrolled with approval from the Medical Monitor.
  • Participant must have received at least 1-2 prior lines of therapy, depending on histological subtype but no more than 7 systemic lines of anti-cancer therapy.

Criteria for both B-ALL, NHL, and CLL/SLL:

  • Eastern Cooperative Oncology Group performance status score of 0 or 1.
  • An estimated life expectancy of at least 12 weeks according to the investigator's judgment.
  • Seronegative for human immunodeficiency virus antibody.
  • Participant has adequate bone marrow, renal, hepatic, pulmonary, and cardiac function.

Key Exclusion Criteria

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.
  • Active uncontrolled autoimmune disease requiring active immunosuppression at the time of Screening (excluding participants needing steroids for physiologic replacement).
  • Participant has received stem cell transplant within 90 days before Screening.
  • Participant has active graft-versus-host disease (GvHD) symptoms.
  • Participant has received a systemic biologic agent for treatment of the disease under study within 28 days of LD, other systemic anti-cancer therapy within 10 days or 5 half-lives (whichever is shorter) of LD, and no pulse steroid for disease control within 3 days of LD.
  • Radiotherapy within 4 weeks before Screening.
  • Presence of pleural/peritoneal/pericardial catheter, as well as permeant biliary and ureteral stents (does not apply to intravenous lines).
  • Participant has received live vaccine within 4 weeks before Screening. Note: Non-live virus vaccines are not excluded.
  • Participant has received CD19-directed therapy other than autologous CD19-directed CAR T therapy within 90 days of the anticipated start date of LD.

Additional criteria apply.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Phase 1 Dose Escalation: Azer-cel Dose Level 1

Azer-cel, 3 x 10^5 CAR T cells per kilogram (kg) body weight.

Route of Administration: Intravenous infusion
Drug: Cyclophosphamide
Specified dose on specified days
Drug: Fludarabine
Specified dose on specified days
Biological: Azer-cel
Infusion of Allogeneic Anti-CD19 CAR T cells
Other Names:
  • Allogeneic Anti-CD19 CAR T cells
  • PBCAR0191
Experimental: Phase 1 Dose Escalation: Azer-cel Dose Level 2

Azer-cel, 1 x 10^6 CAR T cells per kg body weight.

Route of Administration: Intravenous infusion
Drug: Cyclophosphamide
Specified dose on specified days
Drug: Fludarabine
Specified dose on specified days
Biological: Azer-cel
Infusion of Allogeneic Anti-CD19 CAR T cells
Other Names:
  • Allogeneic Anti-CD19 CAR T cells
  • PBCAR0191
Experimental: Phase 1 Dose Escalation: Azer-cel Dose Level 3a

Azer-cel, 3 x 10^6 CAR T cells per kg body weight.

Route of Administration: Intravenous infusion
Drug: Cyclophosphamide
Specified dose on specified days
Drug: Fludarabine
Specified dose on specified days
Biological: Azer-cel
Infusion of Allogeneic Anti-CD19 CAR T cells
Other Names:
  • Allogeneic Anti-CD19 CAR T cells
  • PBCAR0191
Experimental: Phase 1 Dose Escalation: Azer-cel Dose Level 4

Azer-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
Drug: Cyclophosphamide
Specified dose on specified days
Drug: Fludarabine
Specified dose on specified days
Biological: Azer-cel
Infusion of Allogeneic Anti-CD19 CAR T cells
Other Names:
  • Allogeneic Anti-CD19 CAR T cells
  • PBCAR0191
Experimental: Phase 1 Dose Escalation: Azer-cel Dose Level 4b

Azer-cel, 500 x 10^6 CAR T cells (flat dose).

Route of Administration: Intravenous infusion
Drug: Cyclophosphamide
Specified dose on specified days
Drug: Fludarabine
Specified dose on specified days
Biological: Azer-cel
Infusion of Allogeneic Anti-CD19 CAR T cells
Other Names:
  • Allogeneic Anti-CD19 CAR T cells
  • PBCAR0191
Experimental: Phase 1B Dose Expansion: Azer-cel

Azer-cel will be administered at a dose level established in Phase 1.

Route of Administration: Intravenous infusion
Drug: Cyclophosphamide
Specified dose on specified days
Drug: Fludarabine
Specified dose on specified days
Biological: Azer-cel
Infusion of Allogeneic Anti-CD19 CAR T cells
Other Names:
  • Allogeneic Anti-CD19 CAR T cells
  • PBCAR0191
Drug: IL-2
Specified dose on specified days

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Up to Day 720
Phase 1b Dose Expansion: Objective Response Rate (ORR) B-ALL
Time Frame: Up to Day 720
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
Time Frame: Up to Day 720
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of Response (DoR)
Time Frame: Up to day 720
- Defined as the duration (days) from initial response to disease progression or death.
Up to day 720
Progression-free survival (PFS)
Time Frame: Up to day 720
- Defined as the duration (days) from Day 0 to disease progression or death.
Up to day 720
Overall survival (OS)
Time Frame: Up to day 720
- Defined as the duration (days) from Day 0 to death.
Up to day 720
Time to next treatment (TNT)
Time Frame: Up to day 720
- Defined as the duration (days) from Day 0 to institution of next systemic therapy.
Up to day 720
Number of Participants with AEs
Time Frame: Up to day 720
- Defined as all AEs of clinical significance captured on study and specific reporting of DLTs, treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interests (AESIs), and AEs related to study treatment.
Up to day 720
Phase 1 Dose Escalation: ORR
Time Frame: Up to Day 720
  • B-ALL: NCCN 2017 criteria
  • NHL: Lugano classification
Up to Day 720
Complete Response (CR) Rate
Time Frame: Up to day 720
  • B-ALL: NCCN 2017 criteria
  • NHL: Lugano classification
Up to day 720

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imugene Limited

Investigators

  • Study Chair: John Byon, MD, PhD, Imugene Limited

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 11, 2019

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

June 1, 2027

Study Registration Dates

First Submitted

August 20, 2018

First Submitted That Met QC Criteria

September 7, 2018

First Posted (Actual)

September 11, 2018

Study Record Updates

Last Update Posted (Actual)

February 2, 2026

Last Update Submitted That Met QC Criteria

January 28, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PBCAR0191-01

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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