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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)

NCT03666000 · Imugene Limited
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Official title
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)
About this study
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.
Eligibility criteria
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 design
Enrollment target: 135 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2019-03-11
Estimated completion: 2027-06
Last updated: 2026-02-02
Interventions
Biological: Azer-celDrug: FludarabineDrug: CyclophosphamideDrug: IL-2
Primary outcomes
  • 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 (Up to Day 720)
  • Phase 1b Dose Expansion: ORR NHL (Up to Day 720)
Sponsor
Imugene Limited · industry
Contacts & investigators
ContactImugene Clinical Team · contact · info@imugene.com · +1 984 245 0082
ContactImugene Clinical Team · contact · info@imugene.com · +61 2 9423 0881
InvestigatorJohn Byon, MD, PhD · study_chair, Imugene Limited
All locations (23)
Banner MD Anderson Cancer CenterCompleted
Gilbert, Arizona, United States
City of HopeCompleted
Duarte, California, United States
H. Lee Moffitt Cancer CenterRecruiting
Tampa, Florida, United States
Winship Cancer Institute Emory UniversityRecruiting
Atlanta, Georgia, United States
Northside Hospital Cancer InstituteRecruiting
Atlanta, Georgia, United States
University of MarylandRecruiting
Baltimore, Maryland, United States
Tufts Medical CenterRecruiting
Boston, Massachusetts, United States
Dana-Farber Cancer InstituteCompleted
Boston, Massachusetts, United States
Barbara Ann Karmanos Cancer Institute (Wayne State University)Completed
Detroit, Michigan, United States
University of MinnesotaRecruiting
Minneapolis, Minnesota, United States
Weill Cornell Medical College - NY Presbyterian HospitalCompleted
New York, New York, United States
Columbia University Irving Medical Center/New York Presbyterian HospitalRecruiting
New York, New York, United States
Duke UniversityCompleted
Durham, North Carolina, United States
Ohio State UniversityCompleted
Columbus, Ohio, United States
Lifespan Cancer Institute at Rhode Island HospitalRecruiting
Providence, Rhode Island, United States
Baylor University Medical CenterRecruiting
Dallas, Texas, United States
MD AndersonCompleted
Houston, Texas, United States
Medical College of WisconsinRecruiting
Milwaukee, Wisconsin, United States
Royal Prince Alfred HospitalRecruiting
Camperdown, New South Wales, Australia
Liverpool HospitalRecruiting
Liverpool, New South Wales, Australia
Royal Adelaide HospitalRecruiting
Adelaide, South Australia, Australia
St Vincent's Hospital MelbourneRecruiting
Fitzroy, Victoria, Australia
Barwon Health - Andrew Love Cancer CentreRecruiting
Geelong, Victoria, Australia
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) · TrialPath