CAR T Cell Therapy for Brain Cancer

(IMPACT Trial)

Overseen By Marcia Hodik, RN, BSHS

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Florida

Must not be taking: Systemic steroids

Disqualifiers: Prior malignancy, Spinal metastasis, Bulky tumors, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

18 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for brain cancer in children, specifically targeting aggressive tumors known as high-grade gliomas. The trial tests a special type of immune cell therapy, where patients' own T cells (a type of white blood cell) are modified to better target and fight cancer cells. This involves using Ex-Vivo expanded autologous IL-8 receptor (CXCR2) modified CD70 CAR (8R-70CAR) T cells. Participants must be newly diagnosed with high-grade glioma and have a tumor that tests positive for a marker called CD70. The trial focuses on assessing the safety and feasibility of this approach, aiming to offer a new option for children with this challenging condition. As a Phase 1 trial, the research seeks to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you are on systemic steroids or immunosuppressive agents, you may need to discuss this with the study team, as these could affect eligibility.

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

Research has shown that CAR T cell therapies, such as the 8R-70CAR T cells being tested for brain cancer, have been safely used in other studies. These treatments use specially modified immune cells to fight cancer. Studies have found that CAR T cells can be administered safely, although their effectiveness can vary. Some patients might experience side effects, but these are usually manageable. As this is a Phase 1 trial, the primary goal is to determine the treatment's safety and the optimal dose. Consequently, there is limited safety data available. However, similar CAR T cell therapies have been used safely in early studies. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for brain cancer?

Researchers are excited about CAR T cell therapy for brain cancer because it offers a novel approach by using genetically modified T cells to target and attack cancer cells. While most current treatments, like surgery, radiation, and chemotherapy, aim to remove or kill cancer cells directly, this therapy enhances the body's immune response. The treatment involves modifying T cells with a specific receptor, CXCR2, to improve their ability to locate and destroy cancer cells in the brain. This targeted mechanism provides a promising alternative, potentially leading to more effective and less toxic treatment options for brain cancer patients.

What evidence suggests that this treatment might be an effective treatment for brain cancer?

Research has shown that CAR T cell therapy holds promise for treating brain cancers like glioblastoma. This treatment modifies a patient's immune cells to better locate and attack cancer cells. Studies have demonstrated that this method can enhance the immune system's ability to fight tumors. In this trial, participants will receive Ex-Vivo expanded autologous IL-8 receptor (CXCR2) modified CD70 CAR (8R-70CAR) T cells. These cells have been altered to include IL-8 receptors and target CD70 proteins on cancer cells, boosting their tumor-fighting capability. Although results have varied, the treatment has been tested safely, suggesting potential benefits for patients with aggressive brain tumors, including children. ^{1 3 4 5 6}

Who Is on the Research Team?

Ashley Ghiaseddin, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

This trial is for children with high-grade gliomas, a type of brain cancer that expresses CD70. Participants must have enough T cells to modify and be able to handle the cell collection process. Specific criteria will determine eligibility.

Inclusion Criteria

CBC with differential showing: ANC ≥ 1000 cells/mm3, Platelet count ≥ 100,000 cells/mm3, Hemoglobin ≥ 10 g/dl

Negative serum pregnancy test for females of childbearing potential at enrollment

Willingness to use acceptable contraceptive methods for females of childbearing potential and males with female partners of childbearing potential

Exclusion Criteria

Concurrent illness with specific conditions

Pregnant or lactating women

Treatment on other therapeutic clinical protocols within 30 days prior to enrollment

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

PBMCs are collected through peripheral venipuncture and tumor CD70 status is confirmed

2 weeks

Radiation

Standard-of-care chemoradiation is administered

4 weeks

Adjuvant Chemotherapy

Adjuvant chemo with dose-intensified TMZ 75-100 mg/m2/day for up to 3 cycles

9 weeks

CAR T Cell Treatment

8R-70CAR T cells are administered as a single intravenous infusion

1 week

Follow-up

Participants are monitored for safety and effectiveness after CAR T cell infusion

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ex-Vivo expanded autologous IL-8 receptor (CXCR2) modified CD70 CAR (8R-70CAR) T cells

Trial Overview The study tests a new therapy where a patient's own T cells are modified with an IL-8 receptor and CD70 CAR to target glioma cells. It's in phase I, focusing on safety and how well it can be done.

How Is the Trial Designed?

Group I: 8R-70CAR T cells Experimental Treatment 1 Intervention

Cohort 1 will receive 1 x 10\^6 cells/kg. Cohort 2 will receive 1 x 10\^7 cells/kg. Cohort 3 will receive 1 x 10\^8 cells/kg.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

Florida Department of Health

Collaborator

Trials

30

Recruited

13,000+

Florida Department of Health, Live Like Bella

Collaborator

American Brain Tumor Association

Collaborator

Trials

3

Recruited

100+

St. Baldrick's Foundation

Collaborator

Trials

19

Recruited

9,100+

Published Research Related to This Trial

The study found that different designs of B7-H3-specific CAR T-cells showed strong functionality in lab tests, but their effectiveness against gliomas varied significantly in a living model, highlighting the importance of CAR structure.

Successful anti-tumor responses were linked to the presence and activity of macrophages and endogenous T-cells in the tumor immune microenvironment, indicating that both CAR design and the immune context are crucial for effective therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell design dependent remodeling of the brain tumor immune microenvironment identify macrophages as key players that inhibit or promote anti-tumor activity. Haydar, D., Ibañez-Vega, J., Crawford, JC., et al.[2023]

Modifying CAR T-cells to express IL-8 receptors (CXCR1 or CXCR2) significantly improves their ability to migrate to and persist within solid tumors, which is crucial for effective treatment.

In pre-clinical models of aggressive cancers like glioblastoma, ovarian, and pancreatic cancer, this enhanced CAR T-cell therapy led to complete tumor regression and the development of long-lasting immunologic memory.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors. Jin, L., Tao, H., Karachi, A., et al.[2021]

Radiolabeling CAR-T cells with 89Zr-oxine is an effective method that allows for tracking their distribution in the body using PET imaging, while maintaining the cells' viability and functional characteristics for at least 8 days.

The study found that radiolabeled CAR-T cells retain their ability to target and kill IL-13Rα2 positive tumor cells without significant changes in activation or exhaustion markers, indicating that this labeling technique could enhance our understanding of CAR-T cell behavior in vivo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of chimeric antigen receptor modified T cells expressing scFv-IL-13R&#945;2 after radiolabeling with 89Zirconium oxine for PET imaging. Leland, P., Kumar, D., Nimmagadda, S., et al.[2023]

Engineered T cell therapies, like CAR T cells and TCR T cell therapies, have shown remarkable efficacy in treating certain blood cancers, highlighting their potential as a powerful tool in cancer immunotherapy.

However, these therapies also pose unique safety challenges, such as cytokine release syndrome and neurotoxicity, which require careful nonclinical safety assessments to ensure patient safety during development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonclinical safety assessment of engineered T cell therapies. Lebrec, H., Maier, CC., Maki, K., et al.[2022]

CD4+ CAR T cells targeting the IL-13 receptor α2 showed superior long-term antitumor effects against glioblastoma compared to CD8+ CAR T cells, which became exhausted quickly after initial activation.

The study suggests that maintaining a higher proportion of CD4+ CAR T cells in therapy could enhance the effectiveness of CAR T cell treatments for solid tumors like glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity. Wang, D., Aguilar, B., Starr, R., et al.[2019]

Adoptive T cell immunotherapy using CAR T cells targeting the glioma-specific antigen EGFRvIII shows promise in effectively eliminating malignant gliomas, particularly when combined with standard chemotherapy and radiotherapy.

The study outlines a method for generating these CAR T cells and demonstrates their efficacy in a murine model of glioblastoma, suggesting that preconditioning with temozolomide and whole brain irradiation enhances the therapeutic potential of the CAR T cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of CAR T cells for adoptive therapy in the context of glioblastoma standard of care. Riccione, K., Suryadevara, CM., Snyder, D., et al.[2021]

CAR T cells have shown significant clinical effectiveness in treating blood cancers, but their success in solid tumors has been less impressive, highlighting the need for further research in this area.

While CAR T cell therapy can lead to serious side effects like cytokine release syndrome and neurological toxicity, some theoretical risks have not yet been observed in clinical settings, emphasizing the importance of managing known toxicities for safe treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Toxicity and management in CAR T-cell therapy. Bonifant, CL., Jackson, HJ., Brentjens, RJ., et al.[2023]

Engineering CAR T cells to express IL7 and/or Flt3L significantly increased their abundance within glioblastoma tumors, leading to improved overall survival rates of 67% and 50% respectively, compared to only 9% survival with conventional CAR T cells.

This study highlights the potential of using non-lymphodepleting irradiation to enhance CAR T cell therapy effectiveness in heterogeneous tumors, suggesting that combining IL7 or IL7 Flt3L CAR T cells with other immunotherapies could be a promising strategy for treating glioblastoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma. Swan, SL., Mehta, N., Ilich, E., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05353530

NCT05353530 | IL-8 Receptor-modified CD70 CAR T Cell ... Newly diagnosed CD70 positive adult GBM patients who have undergone surgery for maximal debulking will be enrolled in this 3+3 design dose-escalation ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12592620/

CAR-T cells immunotherapy in the treatment of glioblastoma By expanding ex vivo and reintroducing genetically modified T cells, the immune system is effectively rearmed with a pool of tumor-targeted ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S1525001625001789

Review CAR T cell therapy for glioblastoma CAR T cells have been safely administered through both peripheral and locoregional routes but with variable clinical and radiographic efficacy.

4. nature.com nature.com/articles/s41698-024-00753-0

CAR-T cell therapy for the treatment of adult high-grade ... TCR-T cells have demonstrated efficacy in treating melanoma and metastatic colorectal cancer. However, several cancers, such as GBM, ...

5. journals.lww.com journals.lww.com/annals-of-medicine-and-surgery/fulltext/2025/09000/car_t_cell_therapy_for_glioblastoma__advances,.48.aspx

CAR-T cell therapy for glioblastoma: advances, challenges,... Chimeric antigen receptor T (CAR-T) therapy for glioblastoma involves critically evaluating progress, effectiveness, and challenges.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06946680?term=AREA%5BConditionSearch%5D(Cancer)%20AND%20AREA%5BBasicSearch%5D(CXCR2)&rank=7

IL-8 Receptor-modified CD70 CAR T Cell Therapy in ... After tumor CD70 status is confirmed, the 8R-70CAR T cell production will start. 4 weeks (+/- 1) post completion of radiation, pediatric patients, based on ...