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

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - 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.
  • - 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.

Exclusion Criteria:

  • - 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.
  • - 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

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT06964737
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

Ohio State University Comprehensive Cancer Center
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

James B Elder, MD
Principal Investigator Affiliation Ohio State University Comprehensive Cancer Center
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

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
Study Website: View Trial Website
Additional Details

PRIMARY OBJECTIVE:

  • I. 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:
  • I. 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.
  • V. 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:
  • I. 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:
  • I. 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.

Arms & Interventions

Arms

Experimental: Treatment (anti-GARP CAR T cell)

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.

Interventions

Biological: - Anti-GARP Chimeric Antigen Receptor-T Cells

Given intracavitary

Procedure: - Biospecimen Collection

Undergo collection of CSF and blood samples

Procedure: - Chest Radiography

Undergo chest x-ray

Procedure: - Echocardiography Test

Undergo ECHO

Procedure: - Magnetic Resonance Imaging

Undergo MRI

Procedure: - Multigated Acquisition Scan

Undergo MUGA

Procedure: - Pheresis

Undergo apheresis

Procedure: - Surgical Procedure

Undergo surgery and placement of CSF reservoir

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Columbus, Ohio

Status

Recruiting

Address

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210

Site Contact

James B. Elder, MD

[email protected]

614-685-1965

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