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Clinical Trials in the USA / NCT03666000
Recruiting Phase 1

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 · tracked via the Priya Life Science USA tracker
Sponsor
Imugene Limited
Phase
Phase 1
Started
2019-03-11
Last updated
2026-09-08

Condition(s) studied

Non-Hodgkin LymphomaB-cell Acute Lymphoblastic LeukemiaChronic Lymphocytic LeukemiaSmall Lymphocytic Lymphoma

Investigational drug(s) / intervention(s)

Azer-celFludarabineCyclophosphamideIL-2Ibrutinib, Acalabrutinib, Zanubrutinib, or Pirtobrutinib

Azer-cel: Infusion of Allogeneic Anti-CD19 CAR T cells

Fludarabine: Specified dose on specified days

Cyclophosphamide: Specified dose on specified days

IL-2: Specified dose on specified days

Ibrutinib, Acalabrutinib, Zanubrutinib, or Pirtobrutinib: Specified dose on specified days

Study 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.

Eligibility

Sex
ALL
Min age
18 Years
Max age
Healthy 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 and Con-BTKi cohort): For indication with an approved autologous CAR T-cell therapy, participants must be ineligible for or unable to access autologous CAR T-cell therapy. * 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. Participants enrolling into the Con-BTKi cohort must: * Be receiving a BTKi (as a monotherapy or combination therapy) as the last, systemic anti-cancer regimen before study entry. Alternatively, if previously refractory to one or more BTK inhibitor(s) and the last systemic anti-cancer therapy before study entry did not include a BTKi, one of the previous BTK inhibitors may be used. * Have radiologic or clinical disease progression while on the BTKi * Agree to remain on BTKi therapy during the protocol-defined BTKi treatment window * Have been tolerant to BTKi 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.

Primary outcome measure(s)

Trial sites (15)

FacilityCityRegionStatus
H. Lee Moffitt Cancer Center Tampa Florida Recruiting
Winship Cancer Institute Emory University Atlanta Georgia Recruiting
Northside Hospital Cancer Institute Atlanta Georgia Recruiting
University of Maryland Baltimore Maryland Recruiting
Tufts Medical Center Boston Massachusetts Recruiting
University of Minnesota Minneapolis Minnesota Recruiting
Columbia University Irving Medical Center/New York Presbyterian Hospital New York New York Recruiting
Lifespan Cancer Institute at Rhode Island Hospital Providence Rhode Island Recruiting
Baylor University Medical Center Dallas Texas Recruiting
Medical College of Wisconsin Milwaukee Wisconsin Recruiting
Royal Prince Alfred Hospital Camperdown New South Wales Recruiting
Liverpool Hospital Liverpool New South Wales Recruiting
Royal Adelaide Hospital Adelaide South Australia Recruiting
St Vincent's Hospital Melbourne Fitzroy Victoria Recruiting
Barwon Health - Andrew Love Cancer Centre Geelong Victoria Recruiting

More Imugene Limited trials in the USA

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT03666000 on ClinicalTrials.gov ↗ ← All trials in the USA