CAR T Cell Therapy for Brain Cancer

Overseen By Ohio State University Comprehensive Cancer Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Ohio State University Comprehensive Cancer Center

Must not be taking: Bevacizumab, Chemotherapy, Immunosuppressants, others

Disqualifiers: Other malignancies, Autoimmune diseases, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 10

Duration: 6 weeks

30 Participants Needed

Trial Summary

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.

What data supports the effectiveness of this treatment for brain cancer?

Research shows that CAR T cell therapy, which uses a patient's own immune cells to fight cancer, has shown promise in treating aggressive brain tumors like glioblastoma. Although challenges remain, early studies have demonstrated safety and some evidence of disease-modifying activity in brain tumors. ^{1 2 3 4 5}

Is CAR T Cell Therapy safe for brain cancer patients?

CAR T Cell Therapy has shown safety in early clinical experiences for brain tumors, including glioblastoma, and was well tolerated in a small group of patients with CNS tumors. However, the brain's sensitivity and unique environment pose specific safety challenges that need to be addressed. ^{1 2 5 6 7}

How is the CAR T Cell Therapy for Brain Cancer different from other treatments?

This treatment uses genetically engineered T cells to specifically target and attack brain cancer cells, which can cross the blood-brain barrier more effectively than traditional chemotherapy. It offers a novel approach by using the body's own immune cells to fight the cancer, potentially improving treatment outcomes for brain tumors like glioblastoma. ^{1 2 3 8 9}

What is the purpose of this trial?

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.

Research Team

James B Elder, MD

Principal Investigator

Ohio State University Comprehensive Cancer Center

Eligibility Criteria

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

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.

Timeline

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

Treatment Details

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.

Participant Groups

Group I: Treatment (anti-GARP CAR T cell) Experimental Treatment 8 Interventions

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.

Who Is Running the Clinical Trial?

Ohio State University Comprehensive Cancer Center

Lead Sponsor

Trials

350

Recruited

295,000+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locoregional Delivery of CAR-T Cells Is Feasible in Pediatric CNS Tumors. [2022]

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in Chimeric Antigen Receptor (CAR) T-Cell Therapies for the Treatment of Primary Brain Tumors. Mount, CW., Gonzalez Castro, LN.[2022]

Brain tumors are the most common solid tumors in children and the leading cause of cancer-related deaths, highlighting the urgent need for more effective treatments.

Recent advancements in CAR T cell immunotherapy show promise for improving outcomes in pediatric brain cancer, with ongoing research focusing on specific targets and strategies to enhance the effectiveness of this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in CAR T cell immunotherapy for paediatric brain tumours. Rao, P., Furst, L., Meyran, D., et al.[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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma. Liu, Z., Zhou, J., Yang, X., et al.[2023]

Malignant central nervous system tumors are the leading cause of cancer death in children, and while treatments like surgery and chemotherapy can be effective, they often lead to significant neurological and cognitive side effects.

Adoptive cell therapy using CAR T cells shows promise for treating pediatric brain tumors, but challenges such as tumor heterogeneity and the blood-brain barrier limit its effectiveness; recent preclinical studies are exploring ways to enhance the safety and efficacy of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Therapy's Potential for Pediatric Brain Tumors. Thomas, P., Galopin, N., Bonérandi, E., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Locoregional Delivery of CAR-T Cells Is Feasible in Pediatric CNS Tumors. [2022]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Advances in Chimeric Antigen Receptor (CAR) T-Cell Therapies for the Treatment of Primary Brain Tumors. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Advances in CAR T cell immunotherapy for paediatric brain tumours. [2022]

5. England pubmed.ncbi.nlm.nih.gov

CAR T cells for brain tumors: Lessons learned and road ahead. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety and antitumor activity of GD2-Specific 4SCAR-T cells in patients with glioblastoma. [2023]

7. Switzerland pubmed.ncbi.nlm.nih.gov

CAR T Cell Therapy's Potential for Pediatric Brain Tumors. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

CRISPR Screening of CAR T Cells and Cancer Stem Cells Reveals Critical Dependencies for Cell-Based Therapies. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapy in glioblastoma: charging the T cells to fight. [2021]