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

Must not be taking: Anti-cancer agents, Chemotherapy

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: 8 weeks

90 Participants Needed

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 children and young adults with difficult-to-treat brain tumors. Researchers aim to determine if these specially engineered immune cells can safely target and shrink tumors that have not responded well to other treatments. The study includes three groups based on the tumor's location and type, with each group receiving the treatment differently. Suitable candidates for this trial have a central nervous system tumor, such as diffuse midline glioma, and already have a special catheter (a thin tube) in place for treatment delivery. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before enrolling. You must discontinue chemotherapy, immunotherapy, and radiotherapy, and stabilize or reduce corticosteroid treatment to a specific dose before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that B7-H3 CAR T cells have been tested in children and young adults with brain tumors. In a previous study, researchers administered these CAR T cells directly into the brain, and patients generally tolerated the treatment well, experiencing no severe problems.

The trial involved multiple treatments, which remained manageable, suggesting that most side effects were not too serious. However, as this is an early study focused mainly on safety, some unknowns may exist.

For those considering joining a trial with this treatment, it's important to know that safety information is still being collected. Researchers are carefully studying the treatment to ensure its safety for patients. Always consult your doctor or the trial team for the most accurate and personalized advice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CAR T Cell Therapy for pediatric brain cancer because it uses a novel approach in fighting tumors. Unlike traditional treatments like surgery, radiation, and chemotherapy, which can damage surrounding healthy tissue, CAR T cells are engineered to specifically target and destroy cancer cells. This therapy is particularly promising because it can be delivered directly into the tumor cavity or ventricular system, potentially increasing its effectiveness while minimizing systemic side effects. By harnessing the body's own immune system to combat cancer, CAR T Cell Therapy offers a cutting-edge alternative that could lead to more precise and less invasive treatment options for young patients with brain cancer.

What evidence suggests that this trial's treatments could be effective for pediatric brain cancer?

Research has shown that CAR T cell therapy, which targets the B7H3 protein, may help treat children's brain cancers like DIPG. In this trial, participants will receive B7-H3-specific CAR T cells through different delivery methods based on their condition. An earlier study found that patients who received this therapy experienced potential benefits, and repeated doses were administered safely. These CAR T cells are designed to find and attack cancer cells by recognizing the B7H3 protein, often present on these cells. Early results suggest that this treatment can effectively reach and interact with brain tumors, possibly slowing their growth. While more research is needed to confirm its long-term effectiveness, the initial findings are promising. ^{1 2 3 5 6}

Who Is on the Research Team?

Rebecca Ronsley, MD

Principal Investigator

Seattle Children's Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1 to 26 with specific brain tumors like DIPG, DMG, or other recurrent CNS tumors without standard treatment options. They must be able to undergo apheresis (a procedure to collect T cells), have a catheter in their CNS for drug delivery, expect to live at least 8 weeks, have decent performance status scores (Lansky/Karnofsky ≥60), recovered from prior treatments, stable on low-dose steroids, good organ function and lab values.

Inclusion Criteria

I am between 1 and 26 years old.

My brain cancer has returned or is not responding to treatment, or I have DIPG/DMG after finishing standard therapy.

Your blood test results are within the normal range.

Exclusion Criteria

I am currently suffering from a severe infection.

I am currently on cancer treatment drugs.

Pregnant or breastfeeding

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive B7H3-specific CAR T cell therapy delivered via an indwelling catheter into the tumor resection cavity or ventricular system. Treatment involves two courses with weekly or bi-weekly dosing depending on the treatment arm.

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including MRI evaluations and assessment of CAR T cell distribution and disease response.

up to 7 months

Extension

Participants may continue receiving additional courses of CAR T cells if no adverse effects are observed and more T cells are available.

What Are the Treatments Tested in This Trial?

Interventions

• SCRI-CARB7H3(s)

Trial Overview The study tests B7-H3-specific CAR T cell therapy delivered directly into the brain or ventricular system through an indwelling catheter. It's divided into three arms based on tumor location/type. Patients receive two courses of treatment with weekly doses of engineered T cells targeting B7H3-expressing tumor cells. The goal is safe administration and interaction of these CAR T cells with the tumor.

How Is the Trial Designed?

Group I: ARM C (DIPG) Experimental Treatment 1 Intervention

Patients with DIPG for whom CAR T cells will be delivered into the ventricular system

Group II: ARM B (Ventricular System Infusion) Experimental Treatment 1 Intervention

Patients with non-DIPG either infratentorial tumors or leptomeningeal tumors for which the CAR T cells will be delivered into the ventricular system

Group III: ARM A (Tumor Cavity Infusion) Experimental Treatment 1 Intervention

Patients with non-DIPG supratentorial tumors for which CAR T cells will be delivered into the tumor resection cavity

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials

319

Recruited

5,232,000+

Published Research Related to This Trial

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]

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]

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]

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]

Pediatric CNS tumors are the most common solid tumors in children and lead to significant mortality, highlighting the urgent need for new treatment strategies that are less toxic than current methods like chemotherapy and radiation.

Chimeric antigen receptor (CAR) T-cell therapy shows promise for treating pediatric CNS tumors, but challenges such as antigen selection and potential toxicity must be addressed to ensure its safety and efficacy in young patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Road to CAR T-Cell Therapies for Pediatric CNS Tumors: Obstacles and New Avenues. Burns, I., Gwynne, WD., Suk, Y., et al.[2022]

In a study involving 1,926 subjects from 17 clinical trials, patients with acute lymphocytic leukemia (ALL) were found to have a higher risk of severe cytokine release syndrome (sCRS) and severe neurological toxicities (sNTX) compared to those with non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM).

The use of CAR T cells produced with gammaretrovirus vectors containing CD28 sequences was linked to increased rates of sNTX, while administering cytokine-directed therapies and corticosteroids at lower toxicity grades was associated with reduced rates of sCRS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. Foster, M., Negash, Y., Eberhardt, L., et al.[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]

B7-H3 is a promising target for cancer immunotherapy due to its consistent expression in tumors and limited presence in healthy tissues, making it a suitable candidate for CAR-T therapy.

A newly developed anti-B7-H3 CAR-T demonstrated strong anti-tumor activity in vitro and showed sustained proliferation in response to repeated antigen challenges, indicating its potential effectiveness in treating resistant neuroblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel anti-B7-H3 chimeric antigen receptor from a single-chain antibody library for immunotherapy of solid cancers. Birley, K., Leboreiro-Babe, C., Rota, EM., et al.[2022]

B7-H3 is frequently overexpressed in glioblastoma (GBM) and correlates with higher malignancy and poorer survival rates, making it a promising target for treatment.

CAR T cells engineered to target B7-H3 showed significant antitumor effects in both laboratory tests and in animal models, leading to longer survival compared to control groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma. Tang, X., Zhao, S., Zhang, Y., et al.[2020]

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]

Citations

1. nature.com nature.com/articles/s41591-024-03451-3

Intracerebroventricular B7-H3-targeting CAR T cells for ... A total of 23 patients with DIPG enrolled, and 21 were treated with repeated doses of ICV B7-H3 CAR T cells using intra-patient dose-escalation ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04185038

NCT04185038 | Study of B7-H3-Specific CAR T Cell ... This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with autologous CD4+ and CD8+ T cells lentivirally transduced.

3. brainchildbio.com brainchildbio.com/wp-content/uploads/2025/04/BCBio-FDA-Type-B-Meeting-Press-Release-FINAL.pdf

BrainChild Bio, Inc. to clinically advance BCB-276, an ... This potenMally accelerated clinical path for BCB-276 is supported by the promising preliminary safety and efficacy data for SCRI-CARB7H3(s)1 – the research ...

4. cellgenetherapyreview.com cellgenetherapyreview.com/3972-News/617071-BrainChild-Bio-advances-CAR-T-therapy-for-pediatric-brain-tumors/

BrainChild Bio advances CAR-T therapy for pediatric brain ... This potentially accelerated clinical path for BCB-276 is supported by the promising preliminary safety and efficacy data for SCRI-CARB7H3(s) — ...

5. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT04185038/

Clinical Trial: NCT04185038 This is a Phase 1 study of central nervous system (CNS) locoregional adoptive therapy with autologous CD4+ and CD8+ T cells lentivirally transduced.

6. delta.larvol.com delta.larvol.com/Products/?ProductId=cadedd71-6917-4806-8365-605d10633beb

SCRI-CARB7H3(s) / Seattle Children's Hospital, Cellevolve ... A first-in-human phase 1 trial of systemic B7H3 CAR T cells for children and young adults with relapsed/refractory solid tumors.