18 Participants Needed

CAR T Cell Therapy for Brain Cancer

(IMPACT Trial)

MH
Overseen ByMarcia Hodik, RN, BSHS, CCRP
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

What is the purpose of this trial?

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+ pediatric high-grade glioma

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.

What data supports the effectiveness of the treatment Ex-Vivo expanded autologous IL-8 receptor (CXCR2) modified CD70 CAR (8R-70CAR) T cells for brain cancer?

Research shows that modifying CAR T cells with the IL-8 receptor (CXCR2) enhances their ability to move into and persist within tumors, leading to complete tumor regression and long-lasting immune memory in aggressive tumors like glioblastoma in pre-clinical models.12345

Is CAR T cell therapy generally safe for humans?

CAR T cell therapy can cause serious side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). These side effects are known and are being studied to improve safety.13678

What makes the CAR T Cell Therapy for Brain Cancer treatment unique?

This treatment is unique because it uses T cells modified with the IL-8 receptor (CXCR2) to enhance their ability to migrate and persist in the tumor, improving their effectiveness against solid tumors like brain cancer.12349

Research Team

AG

Ashley Ghiaseddin, MD

Principal Investigator

University of Florida

Eligibility Criteria

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
See 13 more

Exclusion Criteria

Concurrent illness with specific conditions
Pregnant or lactating women
Treatment on other therapeutic clinical protocols within 30 days prior to enrollment
See 2 more

Timeline

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

Treatment Details

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.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: 8R-70CAR T cellsExperimental Treatment1 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.

Find a Clinic Near You

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+

Findings from Research

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

References

Bioactivity and Safety of IL13Rα2-Redirected Chimeric Antigen Receptor CD8+ T Cells in Patients with Recurrent Glioblastoma. [2023]
CXCR1- or CXCR2-modified CAR T cells co-opt IL-8 for maximal antitumor efficacy in solid tumors. [2021]
Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity. [2019]
CAR T-cell design dependent remodeling of the brain tumor immune microenvironment identify macrophages as key players that inhibit or promote anti-tumor activity. [2023]
IL7 and IL7 Flt3L co-expressing CAR T cells improve therapeutic efficacy in mouse EGFRvIII heterogeneous glioblastoma. [2023]
Characterization of chimeric antigen receptor modified T cells expressing scFv-IL-13Rα2 after radiolabeling with 89Zirconium oxine for PET imaging. [2023]
Nonclinical safety assessment of engineered T cell therapies. [2022]
Toxicity and management in CAR T-cell therapy. [2023]
Generation of CAR T cells for adoptive therapy in the context of glioblastoma standard of care. [2021]
Unbiased ResultsWe believe in providing patients with all the options.
Your Data Stays Your DataWe only share your information with the clinical trials you're trying to access.
Verified Trials OnlyAll of our trials are run by licensed doctors, researchers, and healthcare companies.
Back to top
Terms of Service·Privacy Policy·Cookies·Security