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.
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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
24
Autologous IL13Rα2-targeted CAR-T cells engineered to secrete anti-PD-L1 antibody will be administered after lymphodepleting pretreatment. The study includes peripheral intravenous infusion alone or peripheral intravenous infusion combined with intraventricular injection. Peripheral dose-escalation levels are 1×10\^6 cells/kg, 3×10\^6 cells/kg, and 1×10\^7 cells/kg. In the combined administration strategy, the intraventricular dose is 20%-30% of the peripheral dose, with adjustment based on patient tolerability. Patients will be monitored in the ICU or a dedicated inpatient setting during infusion and for adverse events including CRS and ICANS after infusion.
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Beijing, Beijing Municipality, China
Incidence of Grade 3 or Higher Treatment-Related Adverse Events
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.
Time frame: From first CAR-T cell infusion through Day 28
Progression-Free Survival
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.
Time frame: Up to 2 years after first CAR-T cell infusion
Incidence and Maximum Grade of Cytokine Release Syndrome
Incidence and maximum grade of cytokine release syndrome following CAR-T cell infusion, graded according to ASTCT consensus criteria.
Time frame: From first CAR-T cell infusion through Day 28
Incidence and Maximum Grade of Immune Effector Cell-Associated Neurotoxicity Syndrome
Incidence and maximum grade of immune effector cell-associated neurotoxicity syndrome following CAR-T cell infusion, graded according to ASTCT consensus criteria.
Time frame: From first CAR-T cell infusion through Day 28
Overall Survival
Overall survival, defined as the time from first CAR-T cell infusion to death from any cause.
Time frame: Up to 2 years after first CAR-T cell infusion
Objective Response Rate by MRI/PET-CT
Objective response rate, defined as the proportion of participants achieving complete response or partial response based on imaging assessment using multimodal MRI and/or PET-CT.
Time frame: Assessed at Day 56, Day 84, and every 3 months thereafter up to 2 years
Change in Tumor Volume on Imaging
Change in tumor volume from baseline measured by multimodal MRI and/or PET-CT.
Time frame: 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
Change from baseline in quality of life as assessed by the EORTC QLQ-C30 questionnaire.
Time frame: Baseline, Day 28, Day 56, Day 84, and every 3 months thereafter up to 2 years
Change in Karnofsky Performance Status Score
Change from baseline in Karnofsky Performance Status score.
Time frame: Baseline, Day 28, Day 56, Day 84, and every 3 months thereafter up to 2 years
Change in Modified Rankin Scale Score
Change from baseline in modified Rankin Scale score.
Time frame: Baseline, Day 28, Day 56, Day 84, and every 3 months thereafter up to 2 years
Persistence of CAR-T Cells in Peripheral Blood
Persistence of IL13Rα2 CAR-T cells in peripheral blood measured by flow cytometry and/or real-time PCR.
Time frame: Baseline and multiple post-infusion time points through 2 years
Persistence of CAR-T Cells in Cerebrospinal Fluid
Persistence of IL13Rα2 CAR-T cells in cerebrospinal fluid, when available, is measured by flow cytometry and/or real-time PCR.
Time frame: Post-infusion time points through 2 years
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