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| ID | Type | Description | Link |
|---|---|---|---|
| 2024-I2M-3-014 | Other Grant/Funding Number | CAMS Innovation Fund for Medical Sciences |
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| Name | Class |
|---|---|
| Pecking Union Medical College Hospital, Department of Neurosurgery | UNKNOWN |
| Emergency General Hospital, Department of Neurosurgery | UNKNOWN |
| Peking University International Hospital | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Single Treatment Arm | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| IL13Rα2 CAR-T Cells Secreting Anti-PD-L1 Antibody | Biological | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | 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. | Up to 2 years after first CAR-T cell infusion |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | From first CAR-T cell infusion through Day 28 |
| Incidence and Maximum Grade of Immune Effector Cell-Associated Neurotoxicity Syndrome |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Ming Yang, Medical Doctor | Contact | +86 138 1065 5237 | yangming@cicams.ac.cn |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College | Beijing | Beijing Municipality | 100021 | China |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41495049 | Background | Li X, Shang X, Liu J, Zhang Y, Jia X, Li H, Wang Y, Gao J, Ma X, Zhang X, Rong X, Gan W, Zhang Y, Chen J, Wang L, Bao Z, He L, Yan X, Liu Y, Shao J, Xiao Z, Wang Z, Zhu H, Wang Z, Wu Y, Huang Y. Intrathecal CRISPR-edited allogeneic IL-13Ralpha2 CAR T Cells for recurrent high-grade Glioma: preclinical characterization and phase I trial. Nat Commun. 2026 Jan 6;17(1):1362. doi: 10.1038/s41467-025-68112-6. | |
| 30519867 |
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At this stage, we have not made definitive plans to share individual participant data (IPD). However, data will be made available to qualified researchers upon request after the completion of the study and publication of the results, subject to applicable privacy and ethical guidelines.
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| ID | Term |
|---|---|
| D005910 | Glioma |
| ID | Term |
|---|---|
| D018302 | Neoplasms, Neuroepithelial |
| D017599 | Neuroectodermal Tumors |
| D009373 | Neoplasms, Germ Cell and Embryonal |
| D009370 | Neoplasms by Histologic Type |
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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.
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Incidence and maximum grade of immune effector cell-associated neurotoxicity syndrome following CAR-T cell infusion, graded according to ASTCT consensus criteria. |
| 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. | 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. | 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. | 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. | 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. | 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. | 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. | 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. | Post-infusion time points through 2 years |
|
| Background |
| Law I, Albert NL, Arbizu J, Boellaard R, Drzezga A, Galldiks N, la Fougere C, Langen KJ, Lopci E, Lowe V, McConathy J, Quick HH, Sattler B, Schuster DM, Tonn JC, Weller M. Joint EANM/EANO/RANO practice guidelines/SNMMI procedure standards for imaging of gliomas using PET with radiolabelled amino acids and [18F]FDG: version 1.0. Eur J Nucl Med Mol Imaging. 2019 Mar;46(3):540-557. doi: 10.1007/s00259-018-4207-9. Epub 2018 Dec 5. |
| 25939063 | Background | Long AH, Haso WM, Shern JF, Wanhainen KM, Murgai M, Ingaramo M, Smith JP, Walker AJ, Kohler ME, Venkateshwara VR, Kaplan RN, Patterson GH, Fry TJ, Orentas RJ, Mackall CL. 4-1BB costimulation ameliorates T cell exhaustion induced by tonic signaling of chimeric antigen receptors. Nat Med. 2015 Jun;21(6):581-90. doi: 10.1038/nm.3838. Epub 2015 May 4. |
| 33030521 | Background | Portnow J, Wang D, Blanchard MS, Tran V, Alizadeh D, Starr R, Dodia R, Chiu V, Brito A, Kilpatrick J, McNamara P, Forman SJ, Badie B, Synold TW, Brown CE. Systemic Anti-PD-1 Immunotherapy Results in PD-1 Blockade on T Cells in the Cerebrospinal Fluid. JAMA Oncol. 2020 Dec 1;6(12):1947-1951. doi: 10.1001/jamaoncol.2020.4508. |
| D009369 | Neoplasms |
| D009375 | Neoplasms, Glandular and Epithelial |
| D009380 | Neoplasms, Nerve Tissue |