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)

Imugene Limited23 个研究点分布在 2 个国家目标入组 135 人开始时间: 2019年3月11日最近更新: 2026年9月8日

适应症

干预措施

试验速览

阶段: 1 期
状态: 招募中
发起方: Imugene Limited
入组人数: 135
试验地点: 23
主要终点: Phase 1 Dose Escalation/Phase 1b Dose Expansion: Number of Participants with Azer-cel-related AEs Defined as Dose-limiting Toxicities (DLTs)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验相关资讯

研究概览

简要总结

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.

详细描述

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.

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Parallel
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•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)
•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)
•FL (Grade 1-3a)
•MZL that is fluorodeoxyglucose (FDG)-avid on positron emission tomography (PET) scan
•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
•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.

排除标准

•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.