CAR T Cell Therapy for Pediatric Brain Cancer

NV
Overseen ByNicholas Vitanza, MD
Age: < 65
Sex: Any
Trial Phase: Phase 1
Sponsor: Seattle Children's Hospital
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 for children and young adults with specific brain tumors that recur or resist standard treatments. It uses HER2-specific CAR T cell locoregional immunotherapy, which modifies a person’s immune cells to better attack cancer cells in the brain. Researchers aim to determine if this treatment, delivered directly into the brain, can safely and effectively target HER2-positive tumors (a specific protein found in some cancer cells). Children or young adults whose brain tumors have returned and tested positive for HER2, and who already have a special catheter in place for treatment, might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking all current medications, but you must stop certain treatments like chemotherapy, biologic therapy, and anti-tumor antibody therapy for specific periods before enrolling. Corticosteroid treatment must be stable or decreasing, with a maximum dose specified.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that HER2-specific CAR T cell therapy could be promising for treating solid tumors, including brain tumors. In these studies, patients generally tolerated the therapy well. For instance, one study found that patients with glioblastoma and other cancers experienced manageable side effects, indicating the treatment is likely safe.

Moreover, similar CAR T cell treatments targeting other proteins have been shown to be safe and potentially effective for some patients. These studies involved administering the treatment directly to the brain, which is similar to the approach in this trial.

As a Phase 1 study, the main focus is on safety and the body's response to the treatment. So far, data suggests that HER2-specific CAR T cell therapy can be administered safely, but careful monitoring remains important with any new treatment.12345

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pediatric brain cancer, which often involve surgery, radiation, and chemotherapy, HER2-specific CAR T Cell Locoregional Immunotherapy introduces a novel approach by harnessing the body's own immune system to target cancer cells. This therapy uses genetically engineered T cells that are designed to specifically attack HER2-positive cancer cells, which is a new mechanism of action compared to traditional methods. The treatment is delivered directly into the tumor site or ventricular system, allowing for a targeted approach that minimizes damage to surrounding healthy tissue. Researchers are excited about this therapy because it offers the potential for a more precise and less invasive treatment, with the hope of improved outcomes and fewer side effects for young patients.

What evidence suggests that HER2-specific CAR T Cell Locoregional Immunotherapy might be an effective treatment for pediatric brain cancer?

Research shows that a new treatment called HER2-specific CAR T cell therapy holds promise for treating brain tumors in children. This trial will evaluate two delivery methods for this therapy. In ARM A, participants with supratentorial tumors will receive CAR T cells directly into the tumor resection cavity. In ARM B, participants with infratentorial or leptomeningeal tumors will receive CAR T cells into the fourth ventricle or lateral ventricle, respectively. This therapy uses specially modified immune cells to target and attack tumor cells with a marker called HER2, often found in certain brain cancers. Early studies suggest that delivering these modified cells directly to the brain is safe and doesn't cause serious side effects. Evidence also indicates that this treatment can help manage progressive glioblastoma, a type of brain cancer. While more research is needed, these early results offer hope for treating challenging brain tumors in children and young adults.23678

Who Is on the Research Team?

RR

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 recurrent or refractory HER2-positive CNS tumors who have no standard therapy options left. They must have a CNS catheter in place, a life expectancy of at least 8 weeks, recovered from previous treatments, stable or decreasing steroid use, good organ function and lab values, not be pregnant or breastfeeding, and agree to use contraception.

Inclusion Criteria

My brain tumor is HER2 positive.
I can undergo apheresis or already have an apheresis product ready for use.
Your lab test results are within the normal range.
See 12 more

Exclusion Criteria

I have been diagnosed with a specific brain tumor known as DIPG.
I have severe heart issues or irregular heartbeats needing treatment.
I am showing signs of a possible herniation.
See 6 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Course 1

Participants receive weekly doses of CAR T cells for three weeks, followed by a week off and an examination period

4 weeks

Treatment Course 2

Participants receive another course of weekly doses of CAR T cells for three weeks

3 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including MRI evaluations

up to 6 months

Extension

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

What Are the Treatments Tested in This Trial?

Interventions

  • HER2-specific CAR T Cell Locoregional Immunotherapy
Trial Overview The study tests HER2-specific CAR T cell therapy delivered through an indwelling CNS catheter over two courses. Each course involves weekly doses for three weeks followed by one week off. The treatment aims to allow engineered T cells to directly interact with tumor cells in the brain.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Group I: ARM B (Ventricular System Infusion)Experimental Treatment1 Intervention
Group II: ARM A (Tumor Cavity Infusion)Experimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

Seattle Children's Hospital

Lead Sponsor

Trials
319
Recruited
5,232,000+

Published Research Related to This Trial

Engineering CAR T cells with a medium-length spacer significantly improves their effectiveness against HER2-positive pediatric CNS tumors, as demonstrated in a medulloblastoma model.
The ongoing BrainChild-01 trial shows that repeated locoregional delivery of HER2-specific CAR T cells in children and young adults is feasible and well tolerated, with initial patients showing no dose-limiting toxicity and signs of local immune activation.
Locoregional infusion of HER2-specific CAR T cells in children and young adults with recurrent or refractory CNS tumors: an interim analysis.Vitanza, NA., Johnson, AJ., Wilson, AL., et al.[2021]
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.
CAR-T cells for pediatric brain tumors: Present and future.Leruste, A., Beccaria, K., Doz, F.[2021]
HER2-specific T cells can effectively recognize and kill HER2-positive medulloblastoma cells, showing significant T-cell activation and proliferation in response to these tumors.
In vivo studies demonstrated that transferring HER2-specific T cells led to sustained regression of established medulloblastomas, suggesting that this approach could be a promising immunotherapy for treating this type of brain tumor.
Regression of experimental medulloblastoma following transfer of HER2-specific T cells.Ahmed, N., Ratnayake, M., Savoldo, B., et al.[2014]

Citations

Study Details | NCT03500991 | HER2-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 to express ...
Advances in CAR T cell immunotherapy for paediatric brain ...Currently, HER2 CAR T cells are being tested in a clinical trial for children with HER2+ brain tumours, over the age of 3 years (NCT02442297). The delivery ...
HER2-Specific CAR T Cells Induce Early Efficacy Without ...Repetitive locoregional infusion of HER2-specific CAR T cells did not induce any dose-limiting toxicities, according to findings from an interim analysis.
Locoregional delivery of IL-13Rα2-targeting CAR-T cells in ...These findings demonstrate that locoregional IL-13Rα2-targeted CAR-T therapy is safe with promising clinical activity in a subset of patients.
CAR-T Therapy for Pediatric High-Grade GliomasCAR-T therapy has shown promise in preclinical model of pHGGs but failed to achieve the same success obtained for hematological malignancies.
CAR T Cell Therapy's Potential for Pediatric Brain Tumors - PMCEPHA2-specific CAR T cell therapy has been proven to be effective and safe in PDOX models of medulloblastoma and ependymomas, even though it is also detected at ...
Literature review: CAR T-cell therapy as a promising ...CAR T-cell therapy offers a promising strategy for targeting HER2-expressing tumours by directly eliminating cancer cells through T-cell ...
Research progress on HER2-specific chimeric antigen ...HER2-CAR-T therapy has shown breakthrough progress in various solid tumors such as glioblastoma (16), breast cancer (17), colorectal cancer (18) ...
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