Recurrent Malignant Glioma
Conditions
Keywords
IL13Rα2 CAR-T, PD-L1-secreting CAR-T, Recurrent Malignant Glioma, Cell Therapy, Immunotherapy
Brief summary
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.
Detailed description
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.
Interventions
BIOLOGICALIL13Rα2 CAR-T Cells Secreting Anti-PD-L1 Antibody
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.
Sponsors
Ming Yang
Pecking Union Medical College Hospital, Department of Neurosurgery
Emergency General Hospital, Department of Neurosurgery
Peking University International Hospital, Department of Neurosurgery
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a multicenter, open-label, non-randomized, single-arm investigator-initiated trial. Eligible patients with recurrent malignant glioma will receive IL13Rα2 CAR-T cells secreting anti-PD-L1 antibody. Two administration strategies are planned within the single-group study framework: peripheral intravenous infusion alone, or peripheral intravenous infusion combined with intraventricular injection, with dose-escalation and safety monitoring.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Grade 3 or Higher Treatment-Related Adverse Events | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Incidence and Maximum Grade of Cytokine Release Syndrome | From first CAR-T cell infusion through Day 28 | Incidence and maximum grade of cytokine release syndrome following CAR-T cell infusion, graded according to ASTCT consensus criteria. |
| Incidence and Maximum Grade of Immune Effector Cell-Associated Neurotoxicity Syndrome | From first CAR-T cell infusion through Day 28 | Incidence and maximum grade of immune effector cell-associated neurotoxicity syndrome following CAR-T cell infusion, graded according to ASTCT consensus criteria. |
| Overall Survival | Up to 2 years after first CAR-T cell infusion | Overall survival, defined as the time from first CAR-T cell infusion to death from any cause. |
| Objective Response Rate by MRI/PET-CT | Assessed at Day 56, Day 84, and every 3 months thereafter up to 2 years | 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. |
| 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 tumor volume from baseline measured by multimodal MRI and/or PET-CT. |
| 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 from baseline in quality of life as assessed by the EORTC QLQ-C30 questionnaire. |
| Change in Karnofsky Performance Status Score | Baseline, Day 28, Day 56, Day 84, and every 3 months thereafter up to 2 years | Change from baseline in Karnofsky Performance Status score. |
| Change in Modified Rankin Scale Score | Baseline, Day 28, Day 56, Day 84, and every 3 months thereafter up to 2 years | Change from baseline in modified Rankin Scale score. |
| Persistence of CAR-T Cells in Peripheral Blood | Baseline and multiple post-infusion time points through 2 years | Persistence of IL13Rα2 CAR-T cells in peripheral blood measured by flow cytometry and/or real-time PCR. |
| Persistence of CAR-T Cells in Cerebrospinal Fluid | Post-infusion time points through 2 years | Persistence of IL13Rα2 CAR-T cells in cerebrospinal fluid, when available, is measured by flow cytometry and/or real-time PCR. |
Countries
China
Contacts
CONTACTMing Yang, Medical Doctor
Outcome results
None listed