CAR T-Cell Therapy for Brain Tumor

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Bevacizumab, Immunosuppressants, others

Disqualifiers: Uncontrolled seizures, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 36

Duration: 4 weeks

27 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 individuals with brain tumors such as recurring glioblastoma or worsening astrocytoma. The goal is to determine if these specially modified immune cells are safe and effective when administered directly to the brain. This trial aims to identify the optimal dose and understand any side effects. Candidates should have a confirmed diagnosis of these brain tumors that have returned or worsened despite prior treatment. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you are on active bevacizumab therapy, you cannot participate in the trial.

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

Research has shown that a new treatment using modified immune cells, called TGFβR2KO/IL13Rα2 CAR T-cells, might be safe and tolerable for treating brain tumors. This treatment involves altering a patient's own immune cells to enhance their ability to locate and attack tumor cells. Some studies suggest that these modified cells can be safely administered directly into the brain. Patients in earlier studies generally tolerated this treatment well, with manageable side effects. However, as this is an early-phase trial, the main focus remains on safety and determining the optimal dose. While early results appear promising, further research is necessary to fully understand the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for brain tumors, which often include surgery, radiation, and chemotherapy, the TGFβR2KO/IL13Rα2 CAR T-Cell therapy targets cancer cells in a novel way. This treatment uses genetically engineered T-cells that are designed to specifically recognize and attack tumor cells expressing the IL13Rα2 protein, which is often found on brain tumor cells. Researchers are excited because this approach harnesses the body's own immune system and delivers the treatment directly to the brain, potentially leading to more precise and effective tumor targeting with fewer side effects compared to traditional therapies. Additionally, the intracranial delivery method could enhance the treatment's ability to penetrate the brain's protective barriers, offering a promising new avenue for combating these challenging tumors.

What evidence suggests that TGFβR2KO/IL13Rα2 CAR T-Cells might be an effective treatment for glioblastoma or IDH-mutant astrocytoma?

Research has shown that a new treatment using modified immune cells, called CAR T-cells, might help treat recurring or worsening brain tumors like glioblastoma. In this trial, participants will receive TGFβR2KO/IL13Rα2 CAR T-cells, which are specially altered in a lab to find and attack tumor cells. Earlier studies have shown promise, with some patients living longer. Specifically, patients with brain tumors experienced improved survival rates, with some studies reporting an average survival increase to about 10.2 months. This treatment enhances the body's immune system to fight cancer more effectively. While more research is needed, early results offer hope for those facing aggressive brain tumors. ^{1 2 4 5 6}

Who Is on the Research Team?

Behnam Badie

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with recurrent or progressive glioblastoma or grade 3/4 IDH-mutant astrocytoma. Participants must have a tumor that has returned after treatment or is worsening. Specific eligibility criteria are not provided, but typically include factors like age, health status, and prior treatments.

Inclusion Criteria

Agreement to allow the use of archival tissue from diagnostic tumor biopsies. If unavailable, exceptions may be granted with study principal investigator (PI) approval

My cancer has returned and grown after treatment and it's been 3 months since my last radiation therapy.

Alanine aminotransferase (ALT) ≤ 2.5 x ULN (to be performed within 14 days prior to leukapheresis unless otherwise stated)

Exclusion Criteria

Prospective participants who, in the opinion of the investigator, may not be able to comply with all study procedures (including compliance issues related to feasibility/logistics)

I am still experiencing side effects from my previous cancer treatment.

History of allergic reactions attributed to compounds of similar chemical or biologic composition to study agent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit (in-person)

Leukapheresis and Surgical Resection

Patients undergo leukapheresis and standard of care surgical resection with or without placement of Rickham catheter

1 week

1 visit (in-person)

Treatment

Patients receive autologous TGFβR2KO/IL13Rα2-CAR T cells intracranially once weekly for up to 4 cycles (28 days)

4 weeks

4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Visits on day 30, months 3, 6, 9, and 12

Long-term Follow-up

Participants are followed yearly for up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• TGFβR2KO/IL13Rα2 CAR T-Cells

Trial Overview The trial tests TGFβR2KO/IL13Rα2 CAR T-cell therapy given intracranially to see if it's safe and effective against certain brain tumors. It involves modifying the patient's own immune cells to attack tumor cells and monitoring the results using various imaging techniques.

How Is the Trial Designed?

Group I: Treatment (TGFβR2KO/IL13Rα2 CAR T-cells) Experimental Treatment 9 Interventions

Patients undergo leukapheresis and standard of care surgical resection with or without placement of Rickham catheter. Starting on day 0, patients receive autologous TGFβR2KO/IL13Rα2-CAR T cells intracranially over approximately 5 minutes QW. Cycles repeat weekly for up to 4 cycles (28 days) in the absence of disease progression or unacceptable toxicity. Patients may receive additional cycles if they continue to meet infusion criteria and have doses available for infusion. Patients also undergo CSF and blood sample collection and fludeoxyglucose F-18 (FDG)-positron emission tomography (PET) and MRI throughout the study. Additionally, patients may undergo echocardiography at screening.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A patient with recurrent multifocal glioblastoma treated with IL13Rα2-targeted CAR T cells showed no severe toxic effects (grade 3 or higher) after multiple infusions over 220 days, indicating a favorable safety profile for this therapy.

The treatment resulted in significant tumor regression in both intracranial and spinal tumors, with a sustained clinical response lasting 7.5 months, alongside increased cytokine and immune cell levels in the cerebrospinal fluid, suggesting effective immune activation against the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. Brown, CE., Alizadeh, D., Starr, R., et al.[2023]

A novel chimeric antigen receptor (CAR) T cell therapy targeting the IL13 receptor α-2 (IL13Rα2) shows promise in treating glioblastoma multiforme (GBM), demonstrating effective tumor cell killing and increased survival in animal models.

While the IL13 dTc therapy effectively targets GBM cells, it also retains some activity against normal cells expressing IL13Rα1, indicating a potential safety concern for systemic administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Suppression of human glioma xenografts with second-generation IL13R-specific chimeric antigen receptor-modified T cells. Kong, S., Sengupta, S., Tyler, B., et al.[2021]

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]

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]

A new preclinical mouse model using D-270 MG xenografts effectively mimics the invasive growth patterns of human glioblastoma (GBM), allowing for better study of potential treatments.

T cells engineered with chimeric antigen receptors targeting the EGFRvIII mutation in GBM were able to migrate to invasive tumor areas, suppress tumor growth, and improve survival in mice, indicating a promising approach for immunotherapy in treating GBM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma. Miao, H., Choi, BD., Suryadevara, CM., et al.[2023]

IL13Rα2 is a promising target for immunotherapy in high-grade gliomas, as it is expressed on both glioma stem-like cancer initiating cells (GSCs) and more differentiated tumor cells, making them both susceptible to treatment.

Genetically engineered IL13Rα2-specific CD8(+) T cells (IL13-zetakine(+) CTLs) effectively recognized and killed IL13Rα2-positive GSCs and differentiated cells in laboratory tests and showed strong antitumor activity in mouse models, suggesting a potential new approach to treat resistant glioma populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem-like tumor-initiating cells isolated from IL13Rα2 expressing gliomas are targeted and killed by IL13-zetakine-redirected T Cells. Brown, CE., Starr, R., Aguilar, B., et al.[2022]

IL13Rα2-specific CAR T cells, designed to target glioblastoma without affecting normal brain tissue, demonstrated effective recognition and destruction of IL13Rα2-positive cancer cells without cross-reactivity to IL13Rα1.

In vivo studies showed that CAR T cells with short spacer regions and specific endodomains significantly improved survival in mice with glioma, indicating their potential as a promising treatment for glioblastoma and similar cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization and Functional Analysis of scFv-based Chimeric Antigen Receptors to Redirect T Cells to IL13Rα2-positive Glioma. Krenciute, G., Krebs, S., Torres, D., et al.[2018]

Citations

1. trials.braintumor.org trials.braintumor.org/trials/NCT06815029

Intracranial Genetically Modified Immune Cells (TGFβR2KO ... 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 TGFβR2KO/IL13Rα2 CAR T ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06815029?term=NCT06815029&rank=1

Study Details | NCT06815029 | Intracranial Genetically ... Giving TGFβR2KO/IL13Rα2 CAR T cells may be safe, tolerable, and/or effective in treating patients with recurrent or progressive glioblastoma or grade 3 or 4 ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2025-00342

Intracranial Genetically Modified Immune Cells ... Giving TGFβR2KO/IL13Rα2 CAR T cells may be safe, tolerable, and/or effective in treating patients with recurrent or progressive, IDH wildtype glioblastoma ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12394108/

Evolving therapeutic strategies in glioblastoma The median overall survival (OS) was 7.7 months, extending to 10.2 months with dual delivery, and increased inflammatory marker levels indicated ...

5. withpower.com withpower.com/trial/car-t-cell-therapy-for-brain-tumor-3bfb9

CAR T-Cell Therapy for Brain Tumor Giving TGFβR2KO/IL13Rα2 CAR T cells may be safe, tolerable, and/or effective in treating patients with recurrent or progressive glioblastoma or grade 3 or 4 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38480922/

Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 ... Intrathecal bivalent CAR T cells targeting EGFR and IL13Rα2 in recurrent glioblastoma: phase 1 trial interim results. Nat Med. 2024 May;30(5): ...