CAR T Cell Therapy for Glioblastoma

(IMPACT Trial)

Overseen By Marcia Hodik, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Florida

Must not be taking: Immunosuppressants

Disqualifiers: HIV, Unstable angina, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

39 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for glioblastoma, an aggressive brain cancer. The treatment uses a patient's own modified immune cells, known as CAR T cells, to target and attack the cancer. Specifically, the trial uses Ex-Vivo expanded autologous IL-8 receptor (CXCR2) modified CD70 CAR (8R-70CAR) T cells. Researchers aim to determine if this approach is safe and feasible for treating glioblastoma. This trial suits adults newly diagnosed with glioblastoma whose tumors test positive for a specific marker called CD70. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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 immunosuppressants or other treatments for autoimmune diseases, you may need to stop them, as these conditions are part of the exclusion criteria.

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

Research shows that a new treatment called 8R-70CAR T cells is being tested for safety and practicality. This treatment aims to help the immune system fight glioblastoma, a type of brain cancer.

In earlier studies, 8R-70CAR T cells showed potential. These cells are specially designed to find and destroy cancer cells more effectively by using a part called the IL-8 receptor, which helps them reach tumors better.

This treatment is in the early stages of testing, meaning researchers are still learning about its safety in humans. Early trials mainly focus on whether the treatment is safe to use and what side effects might occur. While these studies don't yet provide a complete picture of safety, they are crucial first steps in developing new treatments.

Considering joining this trial means contributing to researchers' understanding of the treatment's safety and its potential benefits for others in the future. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for glioblastoma, which often include surgery, radiation, and chemotherapy, CAR T cell therapy offers a novel approach by harnessing the body’s immune system. This treatment is unique because it modifies T cells with an IL-8 receptor (CXCR2) and targets the CD70 protein often found on glioblastoma cells. Researchers are excited about this therapy because it represents a personalized approach, potentially providing a more targeted attack on cancer cells while sparing healthy tissue. The ability to expand these modified T cells ex-vivo means they can be produced in quantities that enhance their effectiveness against tumors.

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

Research has shown that 8R-70CAR T cell therapy could be promising for treating glioblastoma, particularly in patients whose tumors have the CD70 marker. These specially modified T cells are designed to find and attack cancer cells more effectively. Early studies suggest that changes to the IL-8 receptor might help these T cells reach the tumor more easily, potentially improving results. Although researchers are still testing this therapy, early findings from similar trials indicate it might help slow tumor growth. As this is a new treatment, more research is needed to confirm its effectiveness. Participants in this trial will receive different dosages of the 8R-70CAR T cells to determine the most effective and safe dose. ^{1 3 6 7 8}

Who Is on the Research Team?

Ashley Ghiaseddin, MD

Principal Investigator

University of Florida

Are You a Good Fit for This Trial?

Adults over 18 with newly-diagnosed, high-grade glioblastoma without prior brain tumors, who've had a recent surgical resection leaving less than 9 cm2 tumor. They must have CD70 positive and MGMT-unmethylated tumors, good liver and kidney function, stable blood counts, no severe illnesses or immune conditions that could interfere with the treatment. Women of childbearing age must test negative for pregnancy and agree to contraception.

Inclusion Criteria

My tumor is located in the upper part of my brain.

I have been newly diagnosed with a high-grade brain tumor without any previous brain tumor history.

I am able to care for myself but may not be able to do active work.

Exclusion Criteria

I have been cancer-free for over 3 years, except for non-melanoma skin cancer.

I do not have HIV or any diseases that weaken my immune system.

My cancer has spread to the lining of my brain and spine, but it's limited.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemoradiation

Patients undergo standard of care chemoradiation

6-8 weeks

Treatment

Administration of a single dose of 8R-70CAR T cells after completion of radiation

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

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 trial is testing a new therapy using the patient's own T cells that are modified to target IL-8 receptor in CD70+ glioblastoma cells. It aims to evaluate if this personalized cellular therapy is safe and can be feasibly produced for each participant.

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. Cohort 4 will receive Cy/Flu + CAR T cells at established maximum tolerated dose.

Who Is Running the Clinical Trial?

University of Florida

Lead Sponsor

Trials

1,428

Recruited

987,000+

AM Rosen Foundation

Collaborator

Trials

1

Recruited

40+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

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]

CAR T cell therapy targeting the glioblastoma antigen EphA2 shows promise for treating this aggressive brain tumor, as EphA2 is highly expressed in glioblastoma but minimally in normal brain tissue.

Among the evaluated CAR designs, CD28.ζ CAR T cells were chosen for clinical development due to their effective antitumor activity and better safety profile, despite no significant functional differences found between various CAR configurations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optimizing EphA2-CAR T Cells for the Adoptive Immunotherapy of Glioma. Yi, Z., Prinzing, BL., Cao, F., et al.[2020]

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]

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]

The study developed a new cytokine receptor, C7R, that enhances the function of CAR T cells by providing continuous IL7 signaling without the toxic effects associated with external cytokines, improving T-cell proliferation and survival.

C7R-coexpressing CAR T cells showed significant antitumor activity in preclinical models of metastatic neuroblastoma and glioblastoma, indicating that this approach could enhance the effectiveness of T-cell therapies against solid tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Constitutive Signaling from an Engineered IL7 Receptor Promotes Durable Tumor Elimination by Tumor-Redirected T Cells. Shum, T., Omer, B., Tashiro, H., et al.[2022]

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]

Two types of CAR-T cells targeting the EphA2 receptor showed significant anti-glioblastoma (GBM) efficacy in vitro and improved survival in tumor-bearing mice, eliminating 20%-50% of tumors in xenograft models.

The effectiveness of these CAR-T cells is linked to the balance of interferon-γ (IFN-γ) production and CXCR-1/2 expression, with excessive IFN-γ leading to reduced anti-tumor activity due to PD-L1 upregulation in GBM cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Antitumor activity of the third generation EphA2 CAR-T cells against glioblastoma is associated with interferon gamma induced PD-L1. An, Z., Hu, Y., Bai, Y., 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]

The study developed 70R CAR-T cells, which are modified with rabies virus glycoprotein (RVG29), showing enhanced ability to cross the blood-brain barrier (BBB) and effectively target CD70+ glioma cells in both laboratory and mouse models.

70R CAR-T cells not only promoted significant tumor regression in glioma xenografts but also improved the overall health of the mice without causing major side effects, indicating a promising advancement in CAR-T therapy for brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rabies virus glycoprotein 29 (RVG29) promotes CAR-T immunotherapy for glioma. Ji, F., Xu, L., Long, K., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06946680

NCT06946680 | IL-8 Receptor-modified CD70 CAR T Cell ... 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05353530?term=AREA%5BConditionSearch%5D(Cancer)%20AND%20AREA%5BBasicSearch%5D(CXCR2)&rank=6

IL-8 Receptor-modified CD70 CAR T Cell Therapy in ... Biological : Ex-Vivo expanded autologous IL-8 receptor ( CXCR2 ) modified ... Safety of 8R-70CAR T-cell therapy in adult patients with de novo CD70+ GBM ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12401244/

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

4. 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.

5. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/341192

IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ ... IL-8 Receptor-modified CD70 CAR T Cell Therapy in CD70+ Adult Glioblastoma · Eligibility Criteria · Study Plan · Outcome Measures · More Information ...

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 ... Biological : Ex-Vivo expanded autologous IL-8 receptor ( CXCR2 ) modified CD70 CAR (8R-70CAR) T cells ... 8R-70CAR T cells. What is the study measuring? Primary ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6728370/

or CXCR2-modified CAR T cells co-opt IL-8 for maximal ... Here, we demonstrate that IL-8 receptor, CXCR1 or CXCR2, modified CARs markedly enhance migration and persistence of T cells in the tumor, which ...

8. ufhealth.org ufhealth.org/clinical-trials/impact

Phase 1 study of IL-8 Receptor-Modified CD70 CAR T Cell ... This is a phase I study to assess the safety and feasibility of IL-8 receptor modified patient-derived activated CD70 CAR T cell therapy in CD70+ adult ...