A Multicenter, Open-Label, Non-Randomized, Single-Arm Investigator-Initiated Trial to Evaluate the Safety and Efficacy of IL13Rα2 CAR-T Cells Secreting Anti-PD-L1 Antibody in Patients With Recurrent Malignant Glioma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- Incidence of Grade 3 or Higher Treatment-Related Adverse Events
研究概览
简要总结
This clinical study is designed to evaluate the safety and efficacy of IL13Rα2 CAR-T cells secreting anti-PD-L1 antibody in patients with recurrent malignant glioma. This trial is a multicenter, open-label, non-randomized, single-arm investigator-initiated trial (IIT). Patients who have recurrent malignant glioma will receive IL13Rα2 CAR-T cell therapy and will be monitored for safety, adverse events (AEs), and efficacy outcomes, including overall survival (OS) and progression-free survival (PFS). The study will help assess the potential of this innovative therapy in the treatment of glioma and its ability to control tumor growth by targeting both IL13Rα2 and PD-L1.
详细描述
The primary aim of this study is to evaluate the safety and efficacy of IL13Rα2 CAR-T cells secreting anti-PD-L1 antibody for the treatment of recurrent malignant glioma. Malignant gliomas are aggressive brain tumors with limited treatment options and poor prognosis. Immunotherapy, including CAR-T cells, has shown promise in various cancers, but its application in glioma treatment remains under investigation.
This study will involve patients with recurrent glioma who have failed prior treatments. Participants will receive a single infusion of IL13Rα2 CAR-T cells, which are engineered to recognize and target tumor cells expressing IL13Rα2. The CAR-T cells will be combined with the secretion of anti-PD-L1 antibodies, aimed at overcoming the immune checkpoint inhibition in the tumor microenvironment.
Safety will be assessed by monitoring adverse events (AEs) and cytokine release syndrome (CRS). The efficacy will be evaluated by measuring tumor response, progression-free survival (PFS), and overall survival (OS) over a follow-up period of several months. The study will also assess changes in the immune microenvironment, including immune cell infiltration and expression of immune checkpoint markers.
The trial will be conducted across multiple centers, including major hospitals in China. It aims to provide valuable data on the potential of this dual-target CAR-T therapy in treating gliomas and to assess its feasibility as a clinical treatment option.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Recurrent malignant glioma (WHO grade IV)
- •Pathologically confirmed and imaging-defined recurrent glioma
- •ECOG score of 0-2
- •Age >=18 years
- •Male or female
- •Life expectancy >3 months
排除标准
- •Severe immune suppression or autoimmune diseases
- •Severe cardiac, liver, kidney, or other major organ dysfunction
- •Pregnant or breastfeeding women
- •Prior treatment with immune checkpoint inhibitors or other immunotherapies
- •Other conditions posing significant risk to the patient or preventing adherence to the study protocol
研究组 & 干预措施
Single Treatment Arm
Participants with recurrent malignant glioma will receive IL13Rα2 CAR-T cells secreting anti-PD-L1 antibody within a single-arm, open-label study framework. Two administration strategies are planned according to investigator assessment and protocol procedures: peripheral intravenous infusion alone, or peripheral intravenous infusion combined with intraventricular injection. Dose escalation is planned, including 1×10^6 cells/kg, 3×10^6 cells/kg, and 1×10^7 cells/kg for peripheral infusion. For the combined administration strategy, the intraventricular dose is 20%-30% of the peripheral dose, adjusted according to tolerability.
干预措施: IL13Rα2 CAR-T Cells Secreting Anti-PD-L1 Antibody (Biological)
结局指标
主要结局
Incidence of Grade 3 or Higher Treatment-Related Adverse Events
时间窗: From first CAR-T cell infusion through Day 28
Incidence of Grade 3 or higher treatment-related adverse events after infusion of IL13Rα2 CAR-T cells secreting anti-PD-L1 antibody, including serious adverse events. Adverse event severity will be graded according to CTCAE version 5.0.
Progression-Free Survival
时间窗: Up to 2 years after first CAR-T cell infusion
Progression-free survival, defined as the time from first CAR-T cell infusion to documented disease progression or death from any cause, whichever occurs first.
次要结局
- Incidence and Maximum Grade of Cytokine Release Syndrome(From first CAR-T cell infusion through Day 28)
- Incidence and Maximum Grade of Immune Effector Cell-Associated Neurotoxicity Syndrome(From first CAR-T cell infusion through Day 28)
- Overall Survival(Up to 2 years after first CAR-T cell infusion)
- Objective Response Rate by MRI/PET-CT(Assessed at Day 56, Day 84, and every 3 months thereafter up to 2 years)
- Change in Tumor Volume on Imaging(Baseline, Day 7, Day 28, Day 56, Day 84, and every 3 months thereafter up to 2 years)
- Change in Quality of Life Score Measured by EORTC QLQ-C30(Baseline, Day 28, Day 56, Day 84, and every 3 months thereafter up to 2 years)
- Change in Karnofsky Performance Status Score(Baseline, Day 28, Day 56, Day 84, and every 3 months thereafter up to 2 years)
- Change in Modified Rankin Scale Score(Baseline, Day 28, Day 56, Day 84, and every 3 months thereafter up to 2 years)
- Persistence of CAR-T Cells in Peripheral Blood(Baseline and multiple post-infusion time points through 2 years)
- Persistence of CAR-T Cells in Cerebrospinal Fluid(Post-infusion time points through 2 years)
研究者
Ming Yang
Clinical Professor
Cancer Institute and Hospital, Chinese Academy of Medical Sciences