AzTrials
AzTrials

Recurrent Malignant GliomaPhase 1NCT06964737

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

A Phase 1 study testing Anti-GARP Chimeric Antigen Receptor-T Cells, Biospecimen Collection and Chest Radiography in people with Recurrent Malignant Glioma and Recurrent WHO Grade 3 Glioma, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Anti-GARP Chimeric Antigen Receptor-T Cells, Biospecimen Collection and Chest Radiography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
30 participants
Where
1 siteUnited States
Study dates
21 May 2025to 31 May 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 21Show fewer
  • Patient has unifocal disease in one hemisphere and is supratentorial. Lesion and edema can not be located in eloquent locations (e.g., brainstem, pre-/post-central gyrus, visual cortex) or within 2 gyri of motor strip.
  • 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
  • Prior to apheresis and treatment 1 a 2- week washout should be observed
  • Subjects must not have received bevacizumab therapy and are not planned to start such therapy
  • Karnofsky performance score (KPS) ≥ 60
  • Subject is a surgical candidate for surgery for malignant glioma with the intent of resecting >80-90% of the tumor as the ideal treatment option
  • 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
  • Liver function tests within 1.5 x institutional upper limit of normal
  • Women of reproductive potential must have a negative pregnancy test within 7 days of study start. All patients of reproductive potential must use a physician-approved contraceptive and refrain from sperm donation for at least two weeks prior, during, and six months after final T cell infusion. Women must refrain from breastfeeding for six months after final T cell infusion
  • Sufficient venous access, to be confirmed prior to apheresis
  • Life expectancy of greater than 12 weeks
  • PI clinical judgement of patients who will likely complete the trial and are able to maintain stable neurologic symptoms during intervention period

Who cannot join

  • 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
Show all 14Show fewer
  • Patients being treated concurrently (within 14 days prior to study enrollment) with any other investigational agent
  • Examples of other investigational agents that would be exclusionary include supportive care agents
  • 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
  • Recent history (within last 3 months) of uncontrolled seizures

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Ohio State University Comprehensive Cancer Center contact

800-293-5066

OSUCCCclinicaltrials@osumc.edu

United States1 site, 1 recruiting

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

    James B. Elder, MD, 614-685-1965, brad.elder@osumc.edu

    James B. Elder, MD

    Recruiting

Other trials in United States

About this study

Official title: A Phase I, Dose-Escalation Trial of Anti-GARP Chimeric Antigen Receptor-T Cell Therapy in Patients With Recurrent High-Grade Glioma Treated at a Single Medical Center

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.

Read the detailed description

PRIMARY OBJECTIVE:

  1. To assess the safety and feasibility of a CAR T targeting GARP for glioma by defining rate, frequency, and severity of dose limiting toxicities (DLT) following intracavity administration to patients with recurrent glioma, to determine recommended phase II dose (RP2D).

SECONDARY OBJECTIVES:

  1. To describe the adverse event profile of anti-GARP CAR T cell therapy. II. To describe the cytokine levels and immunophenotype in cerebrospinal fluid (CSF) during and following anti-GARP CAR T cell therapy.

III. To describe the duration of anti-GARP CAR T cell persistence and phenotype in CSF.

IV. To describe anti-tumor activity of anti-GARP CAR T cell therapy based on objective response rate (ORR), as measured by established radiological criteria.

  1. To estimate the progression-free survival (PFS) and overall survival (OS) of patients receiving anti-GARP CAR T cell therapy.

VI. For research participants with tumor specimens from primary resections and/or autopsy, describe GARP expression levels pre- and post-treatment and correlate with outcomes.

VII. To describe the frequency and phenotype of anti-GARP CAR T cells and describe GARP expression in resected post-treatment tumor tissue at progression (for patients in whom surgical resection is indicated).

EXPLORATORY OBJECTIVES:

  1. To assess peripheral blood (mononuclear cells, plasma) and CSF for biomarkers that may be associated with response to anti-GARP CAR T cell therapy.

II. To assess archival tissues (primary resection), recurrent tumor, and/or autopsy specimens for biomarkers that may be associated with response to anti-GARP CAR T cell therapy.

III. To assess baseline genetic markers that may be associated with response to anti-GARP CAR T cell therapy.

OTHER EFFICACY OBJECTIVES:

  1. Best overall response, determined via response assessment in neuro-oncology (RANO) criteria.

II. Clinical benefit rate that includes all subjects receiving 5 doses of anti-GARP CAR T cell therapy who demonstrate a complete response (CR), partial response (PR), or stable disease (SD) of at least 6 months duration.

III. Duration of response, calculated as the time from which a response is first observed (CR or PR) until progression or death, whichever occurs first.

IV. Overall survival (OS), calculated from first administration of study drug until death for up to two years after receiving the drug.

OUTLINE: This is a dose-escalation study.

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 echocardiography (ECHO) or multigated acquisition scan (MUGA) at screening and collection of CSF and blood samples, lumbar puncture, chest x-ray and magnetic resonance imaging (MRI) throughout the study.

After completion of study treatment, patients are followed up at 2 weeks then at 3, 4, 6, 8, 12 and 24 months then annually for at least 15 years.

Being tested
Anti-GARP Chimeric Antigen Receptor-T Cells, Biospecimen Collection, Chest Radiography, Echocardiography Test, Magnetic Resonance Imaging
Medical subject headings
Glioma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Anti-GARP Chimeric Antigen Receptor-T CellsBiological

    Also called Anti-GARP CAR T Cells (SY), Anti-GARP CAR T-cells (SY), Anti-GARP CAR-T Cells (SY)

    Given intracavitary

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Specimen Collection

    Undergo collection of CSF and blood samples

  • Chest RadiographyProcedure or surgery

    Also called Chest X-ray

    Undergo chest x-ray

  • Echocardiography TestProcedure or surgery

    Also called EC, Echocardiography

    Undergo ECHO

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Multigated Acquisition ScanProcedure or surgery

    Also called Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan

    Undergo MUGA

  • PheresisProcedure or surgery

    Also called Apheresed, Apheresis, Blood Component Removal, Collection, Apheresis/Leukapheresis

    Undergo apheresis

  • Surgical ProcedureProcedure or surgery

    Also called Operation, Surgery, Surgery Type, Surgery, NOS

    Undergo surgery and placement of CSF reservoir

Study groups in NCT06964737
Study groupRoleWhat they receive
Treatment (anti-GARP CAR T cell)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 30 days after the first dose

Secondary outcomes (8)

  1. Incidence of adverse events

    The rate, frequency and severity will be defined using CTCAE 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.

    Measured: Up to 30 days after last dose of study drug

  2. Cytokine levels and immunophenotype in cerebrospinal fluid (CSF)

    Measured: During and following therapy, assessed up to 15 years

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

    Measured: Up to 15 years

  4. Objective response rate (ORR)

    ORR will be calculated and exact binomial 95% confidence interval (CI) will be provided.

    Measured: Up to 15 years

  5. Progression-free survival (PFS)

    Kaplan-Meier methods will be used to estimate PFS with 95% CI.

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

  6. Overall survival (OS)

    Kaplan-Meier methods will be used to estimate OS with 95% CI.

    Measured: From initiation of therapy to death, assessed up to 15 years

  7. Correlation of GARP expression levels with outcomes

    Relative GARP expression in tumor tissue will be summarized using descriptive statistics.

    Measured: At pre- and post-treatment, assessed up to 24 months

  8. Frequency and phenotype of anti-GARP CAR T cells in tumor tissue

    The level and phenotype of anti-GARP CAR T in tumor tissue will be summarized using descriptive statistics.

    Measured: At progression, assessed up to 15 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 May 2025
  2. Study start21 May 2025
  3. Primary completion31 May 2027 (estimated)
  4. Study completion31 May 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
30 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06964737
Sponsor's protocol ID
OSU-24179
Other IDs
NCI-2025-03042
Status last verified
Oct 2025
First submitted
1 May 2025
Last updated
8 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Wu BX, Kreatsoulas D, Cam H, Bolyard C, Chang Y, Mandula J, Welsh PW, Wang Z, Li A, Weltge P, Reynolds K, Amankwah Y, 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 Dec 1;27(12):3087-3103. doi: 10.1093/neuonc/noaf195.

    PubMed 40873341

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Anti-GARP Chimeric Antigen Receptor-T Cells, Biospecimen Collection and Chest Radiography in people with Recurrent Malignant Glioma and Recurrent WHO Grade 3 Glioma, run by Ohio State University Comprehensive Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ohio State University Comprehensive Cancer Center (800-293-5066, OSUCCCclinicaltrials@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Dose limiting toxicities (time frame: Up to 30 days after the first dose). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06964737, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in