30 Participants Needed

CAR T Cell Therapy for Brain Cancer

OS
Overseen ByOhio State University Comprehensive Cancer Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CAR T-cell therapy for individuals with aggressive brain cancer, specifically grade III or IV gliomas that have recurred after initial improvement. The treatment modifies a person’s immune cells in a lab to better target cancer cells, focusing on a protein called GARP. Participants receive these modified T-cells through an infusion to evaluate the therapy's safety and effectiveness. Candidates include those with a history of high-grade gliomas, confirmed recurrent disease, and who have not taken certain medications like bevacizumab. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking any anti-cancer agents, like chemotherapy, 14 days before starting the study and remain off them during the trial. If you're on steroids, you must be on a low dose (4mg or less per day) and not increasing the dosage. Other medications are not specifically mentioned, so it's best to discuss with the trial team.

Is there any evidence suggesting that anti-GARP CAR T cell therapy is likely to be safe for humans?

Research shows that anti-GARP CAR T-cell therapy might be safe and manageable. Studies have found that CAR T-cell therapy is generally safe for patients with glioblastoma, a type of brain cancer. While the treatment appears safe, its effectiveness can vary. Researchers have safely administered CAR T cells in different ways, including directly to the tumor area. However, the treatment's ability to shrink tumors or slow cancer growth can differ for each person. As this trial is in its early stages, safety remains a primary focus, and researchers will closely monitor any side effects. Prospective participants should consult their doctor to understand the possible risks and benefits.12345

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain cancer, which often involve surgery, radiation, and chemotherapy, anti-GARP CAR T cell therapy offers a novel approach by utilizing a patient's own immune system to fight the cancer. This treatment is unique because it involves engineering T cells to target GARP, a specific protein associated with cancer cells, potentially providing a more precise attack on the tumor. Additionally, the delivery method is innovative, as the modified T cells are infused directly into the brain's cavity, which could enhance their effectiveness and minimize systemic side effects. Researchers are excited about this approach due to its potential to offer a more targeted and less toxic treatment option for brain cancer patients.

What evidence suggests that this treatment might be an effective treatment for brain cancer?

Research suggests that anti-GARP CAR T-cell therapy, which participants in this trial will receive, could help treat recurring severe brain tumors, known as grade III or IV gliomas. This therapy modifies a patient's own immune cells, called T cells, to attack cancer cells. Studies have found that targeting a protein called GARP, present in certain brain tumor cells, can improve treatment outcomes. In animal studies, this therapy successfully treated glioblastoma, a type of brain cancer. Although human studies remain limited, early results show promise for this therapy's ability to combat aggressive brain tumors.13456

Who Is on the Research Team?

JB

James B Elder, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with grade III or IV gliomas, a type of brain tumor, that have returned after initial treatment. Participants must be in good physical condition with adequate organ function and no serious medical issues that would prevent them from undergoing the procedures involved in the trial.

Inclusion Criteria

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
White blood cells (WBC) > 4,000 cells/uL
Hemoglobin (Hgb) > 7 gm/dL
See 12 more

Exclusion Criteria

Patients who have a history of malignancy other than the glioma under investigation in this study, except patients with specific malignancies/treatment characteristics, as determined by the investigator
History of allergy to study products/diluents/emulsions
I have an autoimmune disease or need long-term high-dose steroids or immunosuppressants.
See 3 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks
1 visit (in-person)

Apheresis and Surgery

Patients undergo apheresis and surgery for CSF reservoir placement

14 days
2 visits (in-person)

Treatment

Patients receive anti-GARP CAR T intracavitary infusion on days 14, 21, 28, 35, and 42

6 weeks
5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months
Multiple visits at 2 weeks, 3, 4, 6, 8, 12, and 24 months

Long-term Follow-up

Annual follow-up for at least 15 years to monitor overall survival and long-term effects

15 years

What Are the Treatments Tested in This Trial?

Interventions

  • Anti-GARP Chimeric Antigen Receptor-T Cells
Trial Overview The study is testing anti-GARP CAR T-cell therapy to see if it's safe and effective against recurrent brain tumors. Patients' own immune cells are modified to target tumor cells and then infused back into their body. The process includes tests like MRI and blood collection.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Treatment (anti-GARP CAR T cell)Experimental Treatment8 Interventions

Find a Clinic Near You

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials
350
Recruited
295,000+

Published Research Related to This Trial

Adoptive cell therapies, particularly chimeric antigen receptor (CAR) T-cell therapies, are showing promise in treating aggressive primary brain tumors like glioblastoma and diffuse midline glioma, H3 K27M-mutant, which have been challenging to treat with traditional immunotherapy.
Despite the potential of CAR T-cell therapies, significant challenges remain in their development and implementation for brain tumor patients, indicating that while progress is being made, more work is needed to achieve transformative benefits.
Advances in Chimeric Antigen Receptor (CAR) T-Cell Therapies for the Treatment of Primary Brain Tumors.Mount, CW., Gonzalez Castro, LN.[2022]
Infusion of GD2-specific fourth-generation safety-designed chimeric antigen receptor (4SCAR)-T cells in eight patients with GD2-positive glioblastoma (GBM) was found to be safe and well tolerated, with no severe adverse events reported.
Of the eight patients, four experienced a partial response lasting between 3 to 24 months, indicating that 4SCAR-T cells can exert anti-GBM activity, with a median overall survival of 10 months post-infusion.
Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma.Liu, Z., Zhou, J., Yang, X., et al.[2023]
Intracranial delivery of HER2-targeting CAR-T cells was found to be well tolerated in a small group of 3 patients with central nervous system (CNS) tumors, indicating a potential safe application for this therapy.
This study suggests that targeting HER2 with CAR-T cells could be a promising approach for treating CNS tumors, although further research with larger patient groups is needed to confirm efficacy.
Locoregional Delivery of CAR-T Cells Is Feasible in Pediatric CNS Tumors.[2022]

Citations

NCT06964737 | Anti-GARP Chimeric Antigen Receptor T ...Giving anti-GARP CAR T cell therapy may be safe, tolerable, and/or effective in treating patients with recurrent grade III or IV gliomas. Detailed Description.
Chimeric antigen receptor (CAR) T-cell therapy for ...The therapeutic development of CAR T-cell therapy for GBM presents a dichotomy between delivery modalities and clinical efficacy. Systemic ...
CAR-T cell therapy for the treatment of adult high-grade ...This review discusses the landscape of clinical trials for CAR-T cell therapy targeting brain tumors, highlighting key advancements like novel ...
Review CAR T cell therapy for glioblastomaCAR T cells have been safely administered through both peripheral and locoregional routes but with variable clinical and radiographic efficacy.
Targeting TGFβ docking receptor glycoprotein A repetitions ...GARP expression predicts poor outcomes and is highly enriched in glioma stem cells. Treating murine models of glioblastoma with anti-GARP CAR-T ...
Safety and Efficacy of Chimeric Antigen Receptor T-Cell ...Although CAR T-cell therapy is a relatively safe therapeutic option in patients with glioblastoma, it shows marginal efficacy, suggesting that further research ...
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