Treatment of recurrent high-grade gliomas using anti-GARP CAR T cell therapy
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 study is testing a new type of CAR T cell therapy to see if it can safely help people with recurring high-grade gliomas fight their tumors better.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 30 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Ohio State University Comprehensive Cancer Center Academic / other |
| Drugs / interventions | bevacizumab, CAR T, chemotherapy, chimeric antigen receptor |
| Locations | 1 site (Columbus, Ohio) |
| Trial ID | NCT06964737 on ClinicalTrials.gov |
What this trial studies
This phase I trial evaluates the safety, side effects, and optimal dosage of anti-GARP chimeric antigen receptor (CAR) T cell therapy for patients with recurrent grade III or IV gliomas. The approach involves modifying a patient's T cells in the laboratory to target and attack tumor cells expressing the GARP protein. The study will assess the therapy's feasibility, adverse effects, and its effectiveness in improving patient outcomes, including progression-free and overall survival rates. Additionally, it will explore the persistence of CAR T cells and their impact on tumor characteristics post-treatment.
Who should consider this trial
Good fit: Ideal candidates are adults aged 18 and older with a diagnosis of recurrent malignant glioma, specifically WHO grade III or IV.
Not a fit: Patients with low-grade gliomas or those who have received bevacizumab therapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this therapy could provide a novel and effective treatment option for patients with recurrent high-grade gliomas.
How similar studies have performed: While CAR T cell therapies have shown promise in other cancers, this specific approach targeting GARP in gliomas is novel and has not been extensively tested.
Eligibility criteria
Show full 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 * 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 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 * Recent history (within last 3 months) of uncontrolled seizures
Where this trial is running
Columbus, Ohio
- Ohio State University Comprehensive Cancer Center — Columbus, Ohio, United States (Recruiting)
Study contacts
- Principal investigator: James B Elder, MD — Ohio State University Comprehensive Cancer Center
- Study coordinator: Ohio State University Comprehensive Cancer Center
- Email: OSUCCCclinicaltrials@osumc.edu
- Phone: 800-293-5066
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.