CAR T Cell Therapy for Pediatric Brain Cancer

Overseen By Rebecca Ronsley, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Seattle Children's Hospital

Disqualifiers: Cardiac dysfunction, Immunodeficiency, Active infection, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 14 weeks

72 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial uses a patient's own modified immune cells to treat aggressive brain tumors in children and young adults. The immune cells are enhanced to better recognize and attack cancer cells in the brain. This approach has shown remarkable results in treating certain cancers and is now being explored for brain tumors.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you must stop certain treatments like chemotherapy, immunotherapy, and radiotherapy before enrolling, and corticosteroid treatment must be stable or decreasing.

What data supports the effectiveness of the treatment SC-CAR4BRAIN for pediatric brain cancer?

Research shows that CAR T cell therapy, which is a type of treatment that uses modified immune cells to target cancer, has shown some positive responses in early trials for pediatric brain tumors. Additionally, targeting B7-H3, a protein found on many cancer cells, with CAR T cells has shown strong activity in preclinical studies against pediatric brain tumors. ^{1 2 3 4 5}

What safety data exists for CAR T cell therapy in pediatric brain cancer?

In early clinical trials for CAR T cell therapy in children with brain tumors, there were no severe dose-limiting toxicities reported. Some patients experienced expected side effects like low blood cell counts and mild issues such as headaches and liver enzyme changes, but these were manageable. ^{1 2 6 7 8}

What makes the SC-CAR4BRAIN treatment unique for pediatric brain cancer?

The SC-CAR4BRAIN treatment is unique because it uses genetically engineered T cells that target specific proteins (B7-H3, EGFR806, HER2, and IL13) found on brain tumor cells, and it can be delivered directly to the brain, potentially improving effectiveness and reducing side effects compared to traditional treatments like surgery, chemotherapy, and radiotherapy. ^{1 2 3 7 9}

Research Team

Rebecca Ronsley, MD

Principal Investigator

Seattle Children's Hospital

Rebecca Ronsley, MD

Principal Investigator

Seattle Children's Hospital

Eligibility Criteria

This trial is for children and young adults with specific brain tumors like DIPG, DMG, or recurrent/refractory CNS tumors. They must have a life expectancy of at least 8 weeks, be in good physical condition (Lansky/Karnofsky score ≥ 60), have proper organ function, agree to use contraception if applicable, and have a catheter placed for treatment delivery.

Inclusion Criteria

I am between 1 and 26 years old, or between 12 and 26 for the first 3 subjects.

My brain or spinal cord disease is not responding to treatment and there are no standard treatments left.

I have recovered from the side effects of my previous cancer treatments.

Exclusion Criteria

I am currently suffering from a severe infection.

Unwilling to provide consent/assent for study participation

I have a condition that affects my immune system or bone marrow.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SC-CAR4BRAIN infusions via an indwelling catheter into the ventricular system

14 weeks

Multiple visits for infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Extension

Participants may continue to receive additional courses of CAR T infusions if criteria are met

Long-term

Treatment Details

Interventions

• SC-CAR4BRAIN

Trial Overview The study tests SC-CAR4BRAIN therapy using the patient's own T cells engineered to target tumor cells via CARs that recognize B7-H3, EGFR806, HER2, and IL13-zetakine. The modified T cells are delivered directly into the brain through a catheter. Patients are divided into two groups based on their type of tumor.

Participant Groups

Group I: Arm B - DMG & recurrent/refractory tumors Experimental Treatment 1 Intervention

Group II: Arm A - DIPG Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Findings from Research

CAR-T cell therapy, while currently approved only for B cell malignancies, shows promising potential for treating pediatric brain tumors, with early clinical trials indicating some positive responses.

Recent preclinical studies have identified new tumor antigens and combination strategies that enhance the effectiveness of CAR-T cells, particularly when administered directly to the tumor site.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T cells for pediatric brain tumors: Present and future. Leruste, A., Beccaria, K., Doz, F.[2021]

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]

In a study of 49 pediatric brain tumor patient-derived xenografts, B7-H3 was identified as a promising target for CAR T-cell therapy due to its high and consistent expression across various tumor types, while HLA class I expression was found in all high-grade gliomas but only in 57.1% of other tumor subtypes.

B7-H3-CAR T cells demonstrated effective tumor recognition and induced significant tumor regression in both in vitro and in vivo models, suggesting a potential survival advantage for patients with pediatric brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell-surface antigen profiling of pediatric brain tumors: B7-H3 is consistently expressed and can be targeted via local or systemic CAR T-cell delivery. Haydar, D., Houke, H., Chiang, J., 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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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

B7-H3 CAR T cells have shown significant antitumor activity in various pediatric solid tumor models, including osteosarcoma and medulloblastoma, indicating their potential as a treatment option for relapsed pediatric malignancies.

The effectiveness of B7-H3 CAR T cells is linked to the density of the B7-H3 antigen on tumor cells, suggesting that this therapy could be selectively effective against tumors with high antigen expression while minimizing effects on normal tissues with lower expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors. Majzner, RG., Theruvath, JL., Nellan, A., et al.[2021]

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]

Adoptive cell therapy using CAR T cells has shown great success in treating B-cell malignancies, leading to FDA approval, but has faced challenges in effectively targeting pediatric solid tumors and brain tumors due to factors like varied antigen expression and a hostile tumor environment.

The review discusses ongoing strategies to improve the effectiveness of CAR T-cell therapy for solid tumors, highlighting the need to enhance T cell migration to tumor sites and overcome the immunosuppressive conditions present in these tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Landscape of CAR T Cells Beyond Acute Lymphoblastic Leukemia for Pediatric Solid Tumors. DeRenzo, C., Krenciute, G., Gottschalk, S.[2022]

In a phase I clinical trial involving six pediatric brain tumor patients, IL13BBζ-CAR T cell therapy showed promise, with three out of five evaluable patients experiencing transient benefits, although these did not meet the strict criteria for response.

The therapy was well-tolerated, with no dose-limiting toxicities reported, and serious adverse events were minimal, suggesting a favorable safety profile for this innovative treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Expansion of endogenous T cells in CSF of pediatric CNS tumor patients undergoing locoregional delivery of IL13R〿2-targeting CAR T cells: an interim analysis. Wang, L., Oill, AT., Blanchard, M., et al.[2023]

Atypical teratoid/rhabdoid tumors (ATRTs) express the B7-H3 protein, which is crucial for their growth and can be targeted for therapy, highlighting its potential as a therapeutic target for this aggressive pediatric cancer.

Using B7-H3-targeted CAR T cells delivered directly into the brain showed faster and more effective tumor suppression in mouse models compared to traditional intravenous delivery, suggesting that localized treatment may reduce systemic side effects and improve outcomes for children with ATRT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors. Theruvath, J., Sotillo, E., Mount, CW., et al.[2022]

References

1. France pubmed.ncbi.nlm.nih.gov

CAR-T cells for pediatric brain tumors: Present and future. [2021]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Cell-surface antigen profiling of pediatric brain tumors: B7-H3 is consistently expressed and can be targeted via local or systemic CAR T-cell delivery. [2023]

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

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

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

CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

The Landscape of CAR T Cells Beyond Acute Lymphoblastic Leukemia for Pediatric Solid Tumors. [2022]

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

Expansion of endogenous T cells in CSF of pediatric CNS tumor patients undergoing locoregional delivery of IL13R〿2-targeting CAR T cells: an interim analysis. [2023]

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

Locoregionally administered B7-H3-targeted CAR T cells for treatment of atypical teratoid/rhabdoid tumors. [2022]