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RecruitingInterventionalPhase 1

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)

NCT ID: NCT03666000Sponsor: Imugene LimitedLast updated: 2026-02-02

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

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (18)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234

Completed

City of Hope

Duarte, California, 91010

Completed

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612

Recruiting
Clinical Research · Contact
Bijal Shah, MD · Principal Investigator

Winship Cancer Institute Emory University

Atlanta, Georgia, 30322

Recruiting
Clinical Trials · Contact
Edmund Waller, MD · Principal Investigator

Northside Hospital Cancer Institute

Atlanta, Georgia, 30342

Recruiting
Clinical Trials · Contact
Scott Solomon, MD · Principal Investigator

University of Maryland

Baltimore, Maryland, 21201

Recruiting
Clinical Trials · Contact
Jean Yared, MD · Principal Investigator

Tufts Medical Center

Boston, Massachusetts, 02111

Recruiting
Clinical Trials · Contact
Andreas Klein, MD · Principal Investigator

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215

Completed

Barbara Ann Karmanos Cancer Institute (Wayne State University)

Detroit, Michigan, 48201

Completed

University of Minnesota

Minneapolis, Minnesota, 55455

Recruiting
Clinical Research · Contact
Supriya Gupta, MD · Principal Investigator

Weill Cornell Medical College - NY Presbyterian Hospital

New York, New York, 10021

Completed

Columbia University Irving Medical Center/New York Presbyterian Hospital

New York, New York, 10032

Recruiting
Clinical Trials · Contact
Ran Reshef, MD · Principal Investigator

Duke University

Durham, North Carolina, 27708

Completed

Ohio State University

Columbus, Ohio, 43210

Completed

Lifespan Cancer Institute at Rhode Island Hospital

Providence, Rhode Island, 02903

Recruiting
Clinical Trials · Contact
Adam Olszewski, MD · Principal Investigator

Baylor University Medical Center

Dallas, Texas, 75246

Recruiting
Clinical Trials · Contact
Houston Holmes III, MD · Principal Investigator

MD Anderson

Houston, Texas, 77030

Completed

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

Recruiting
Clinical Trials · Contact
Nirav Shah, MD · Principal Investigator