Anti-GARP Chimeric Antigen Receptor T Cell Therapy for the Treatment of Recurrent Grade III or IV Gliomas

NCT06964737 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-24179NCI-2025-03042
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial tests the safety, side effects, and best dose of anti-glycoprotein-A repetitions predominant (GARP) chimeric antigen receptor (CAR) T cell therapy and how well it works in treating patients with grade III or IV gliomas that have come back after a period of improvement (recurrent). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein, such as GARP, on the patient's tumor cells is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain tumors. Giving anti-GARP CAR T cell therapy may be safe, tolerable, and/or effective in treating patients with recurrent grade III or IV gliomas.

Conditions

Recurrent Malignant Glioma; Recurrent WHO Grade 3 Glioma; Recurrent WHO Grade 4 Glioma; WHO Grade 2 Glioma; WHO Grade 3 Glioma; WHO Grade 4 Glioma

Outcome Measures

Primary Outcomes (1)

• Dose limiting toxicities

  The rate, frequency and severity will be defined using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5. Will be summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

  Up to 30 days after the first dose

Secondary Outcomes (8)

• Incidence of adverse events

  Up to 30 days after last dose of study drug

• Cytokine levels and immunophenotype in cerebrospinal fluid (CSF)

  During and following therapy, assessed up to 15 years

• Duration of anti-glycoprotein-A repetitions predominant (GARP) chimeric antigen receptor (CAR) T cell persistence and phenotype in CSF

  Up to 15 years

• Objective response rate (ORR)

  Up to 15 years

• Progression-free survival (PFS)

  From initiation of therapy to the time of progression or death, assessed up to 15 years

Study Arms (1)

Treatment (anti-GARP CAR T cell)

EXPERIMENTAL

Patients undergo apheresis on day -14 and undergo surgery and placement of CSF reservoir on day 0. Patients receive anti-GARP CAR T intracavitary infusion on day 14, 21, 28, 35 and 42 in the absence of disease progression or unacceptable toxicities. Additionally, patients undergo ECHO or MUGA at screening and collection of CSF and blood samples, lumbar puncture, chest x-ray and MRI throughout the study.

Biological: Anti-GARP Chimeric Antigen Receptor-T Cells; Procedure: Biospecimen Collection; Procedure: Chest Radiography; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan; Procedure: Pheresis; Procedure: Surgical Procedure

Interventions

Anti-GARP Chimeric Antigen Receptor-T Cells BIOLOGICAL

Given intracavitary

Also known as: Anti-GARP CAR T Cells (SY), Anti-GARP CAR T-cells (SY), Anti-GARP CAR-T Cells (SY)

Treatment (anti-GARP CAR T cell)

Biospecimen Collection PROCEDURE

Undergo collection of CSF and blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (anti-GARP CAR T cell)

Chest Radiography PROCEDURE

Undergo chest x-ray

Also known as: Chest X-ray

Treatment (anti-GARP CAR T cell)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Treatment (anti-GARP CAR T cell)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (anti-GARP CAR T cell)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Treatment (anti-GARP CAR T cell)

Pheresis PROCEDURE

Undergo apheresis

Also known as: Apheresed, Apheresis, Blood Component Removal, Collection, Apheresis/Leukapheresis, Hemapheresis

Treatment (anti-GARP CAR T cell)

Surgical Procedure PROCEDURE

Undergo surgery and placement of CSF reservoir

Also known as: Operation, Surgery, Surgery Type, Surgery, NOS, Surgical, Surgical Intervention, Surgical Interventions, Surgical Procedures, Type of Surgery

Treatment (anti-GARP CAR T cell)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients are ≥ 18 years old
• Capacity to understand and willingness to provide written informed consent
• Diagnosis or clinical suspicion of recurrent malignant glioma, including:
• History of high-grade glioma (World Health Organization \[WHO\] grade III or IV), or
• Prior, histologically-confirmed diagnosis of grade II glioma with new radiographic findings consistent with a high-grade glioma
• Imaging and/or histopathological confirmation of recurrent disease, or verification of "high risk" histology confirmed by a biopsy with measurable disease by the Radiologic Assessment in Neuro-Oncology (RANO) criteria
• Disease in one hemisphere and is supratentorial
• If on steroids such as dexamethasone, must be on a low dose (≤ 4mg per day) at the time of treatment, and not at an ascending dosage schedule at time of enrollment/leukapheresis
• Subjects must not have received bevacizumab therapy and are not planned to start such therapy
• Karnofsky performance score (KPS) ≥ 60
• Surgical candidate for surgery for malignant glioma
• White blood cells (WBC) \> 4,000 cells/uL
• Hemoglobin (Hgb) \> 7 gm/dL
• Platelets (Plt) \> 100/dL
• Serum creatinine ≤ 1.5 x institutional upper limit of normal

You may not qualify if:

• Patients who have a history of malignancy other than the glioma under investigation in this study, except patients with the following malignancies/treatment characteristics, who are eligible at the investigator's discretion:
• Patients with a history of malignancy that has been treated with curative intent at least 2 years prior to screening and with no evidence of relapse, if no concurrent anti-cancer therapy (except hormonal therapy) is being given
• Patients with a history of malignancy with a negligible risk of metastasis or death (e.g., 5-year OS rate \> 90%) such as adequately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, localized prostate cancer, ductal carcinoma in situ, or stage I uterine cancer
• Patients who have prostate cancer with no evidence of metastatic disease and are not on active therapy, except anti-androgen therapy
• History of autoimmune disease, or other diseases require long-term administration of high-dose steroids \[\> 10 mgs/day\] or immunosuppressive therapies
• Research participants who received steroids must have either received their last dose of steroids 7 days or more prior to apheresis or have dosage tapered to \< 2mg/kg/day
• Patients being treated concurrently (within 14 days prior to study enrollment) with any other investigational agent
• Patients receiving anti-cancer agents such as chemotherapy (e.g., temozolomide) must stop treatment 14 days prior to undergoing apheresis and remain off therapy throughout the duration of CAR T therapeutic intervention
• Patients with active fungal, bacterial, viral, or other infection that requires intravenous antimicrobials
• Prophylactic antimicrobials are allowed
• Patients with active invasive fungal infection should be excluded even if the treatment is oral antimicrobials
• History of allergy to study products/diluents/emulsions

Sponsors & Collaborators

• Ohio State University Comprehensive Cancer Center: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Publications (1)

• Wu BX, Kreatsoulas D, Cam H, Bolyard C, Chang Y, Mandula J, Welsh PW, Wang Z, Li A, Weltge P, Elder JB, Giglio P, Otero JJ, Rajappa P, Gerald D, Chung D, Ma Q, Velegraki M, Li Z. Targeting TGFbeta docking receptor Glycoprotein A Repetitions Predominant (GARP) via novel chimeric antigen receptor (CAR)-T cell platform to treat glioblastoma. Neuro Oncol. 2025 Aug 27:noaf195. doi: 10.1093/neuonc/noaf195. Online ahead of print.

  PMID: 40873341 DERIVED

Related Links

• The Jamesline

MeSH Terms

Conditions

Glioma

Interventions

Specimen Handling; X-Rays; Magnetic Resonance Spectroscopy; Blood Component Removal; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Spectrum Analysis; Chemistry Techniques, Analytical; Therapeutics

Study Officials

• James B Elder, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCclinicaltrials@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 1, 2025
• First Posted: May 9, 2025
• Study Start: May 21, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: October 29, 2025

Record last verified: 2025-10

Locations

US (1)