65 Participants Needed

Genetically Modified T-cell Therapy for Brain Cancer

Recruiting at 1 trial location
Age: Any Age
Sex: Any
Trial Phase: Phase 1
Sponsor: City of Hope Medical Center
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

Trial Summary

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there are specific waiting periods after certain chemotherapy treatments before you can start the trial, such as 6 weeks for nitrosourea-containing regimens and 4 weeks for bevacizumab.

What data supports the effectiveness of the treatment Genetically Modified T-cell Therapy for Brain Cancer?

Research shows that IL13Rα2-specific CAR T cells, which are part of this treatment, have demonstrated significant anti-tumor activity and improved survival in animal models of glioblastoma (a type of brain cancer). These T cells specifically target the IL13Rα2 protein found on tumor cells, leading to effective tumor cell killing without affecting normal brain tissue.12345

What safety data exists for IL13Ralpha2-specific CAR T cell therapy in humans?

IL13Ralpha2-specific CAR T cell therapy has been studied for its safety, particularly focusing on its ability to target cancer cells without affecting normal tissues. Research indicates that certain designs of these CAR T cells can selectively target tumor cells with minimal off-target effects, which is important for safety. However, like other CAR T cell therapies, there is a potential risk of severe side effects such as cytokine release syndrome and neurotoxicity, which are influenced by the specific structural components of the CAR T cells.12346

What makes the IL13Ralpha2-specific CAR T cell treatment unique for brain cancer?

This treatment is unique because it uses genetically modified T cells that specifically target the IL13Ralpha2 protein, which is commonly found in glioblastoma (a type of brain cancer) but not in normal brain tissue. The inclusion of the 4-1BB costimulatory domain enhances the selectivity and effectiveness of these T cells, making them more potent against tumors while reducing the risk of attacking healthy cells.13478

What is the purpose of this trial?

This phase I trial studies the side effects and best dose of genetically modified T-cell immunotherapy in treating patients with malignant glioma that has come back (recurrent) or has not responded to therapy (refractory). A T cell is a type of immune cell that can recognize and kill abnormal cells in the body. T cells are taken from the patient's blood and a modified gene is placed into them in the laboratory and this may help them recognize and kill glioma cells. Genetically modified T-cells may also help the body build an immune response against the tumor cells.

Research Team

BB

Behnam Badie

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

This trial is for patients with malignant glioma that has returned or hasn't responded to treatment. They must have had progression after initial radiation, be able to consent, not need excessive steroids during therapy, and meet specific blood and organ function criteria. Pregnant women can't participate, nor those needing dialysis, with other active cancers, severe infections or major surgery recovery.

Inclusion Criteria

Platelets >= 100,000/dl
International normalized ratio (INR) < 1.3
White blood cell (WBC) > 2,000/dl or Absolute neutrophil count (ANC) > 1,000
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Exclusion Criteria

You need help to support your blood pressure or have heart rhythm problems that cause symptoms.
Research participants with any non-malignant intercurrent illness which is either poorly controlled with currently available treatment, or which is of such severity that the investigators deem it unwise to enter the research participant on protocol shall be ineligible
You need to undergo dialysis treatment.
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Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive genetically modified T-cell immunotherapy in a dose-escalation study with initial low dose followed by higher doses in subsequent cycles.

11 months
Multiple infusions over cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at 4 weeks, 3, 6, 8, 10, and 12 months, and then yearly for 15 years.

15 years
Regular follow-up visits

Treatment Details

Interventions

  • IL13Ralpha2-specific Hinge-optimized 41BB-co-stimulatory CAR Truncated CD19-expressing Autologous T-Lymphocytes
  • IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells
Trial Overview The trial tests genetically modified T-cells designed to target and kill glioma cells in the brain. Patients' own T-cells are engineered in a lab to recognize tumor cells better. The study also includes MRI scans and quality-of-life assessments to monitor effects.
Participant Groups
5Treatment groups
Experimental Treatment
Group I: Arm 5 (Tn/mem-derived CAR T cells, Dual delivery: both ICTb/r AND ICV)Experimental Treatment5 Interventions
Arm 5 (Tn/mem-derived CAR T cells, Dual delivery: both ICTb/r AND ICV)
Group II: Arm 4 (Tcm-derived CAR T cells, Dual delivery: both ICTb/r AND ICV)Experimental Treatment5 Interventions
Arm 4 (Tcm-derived CAR T cells, Dual delivery: both ICTb/r AND ICV)
Group III: Arm 3 (Tcm-derived CAR T cells, Intraventricular [ICV])Experimental Treatment5 Interventions
Arm 3 (Tcm-derived CAR T cells, Intraventricular \[ICV\])
Group IV: Arm 2 (Tcm-derived CAR T cells, ICTb/r)Experimental Treatment5 Interventions
Arm 2 (Tcm-derived CAR T cells, Intratumoral a/f biopsy \[ICTb\] or Intracavitary a/f resection \[ICTr\])
Group V: Arm 1 (Tcm-derived CAR T cells, Intratumoral a/f biopsy [ICTb])Experimental Treatment5 Interventions
Arm 1 (Tcm-derived CAR T cells, Intratumoral a/f biopsy \[ICTb\]

IL13Ralpha2-specific Hinge-optimized 41BB-co-stimulatory CAR Truncated CD19-expressing Autologous T-Lymphocytes is already approved in United States for the following indications:

🇺🇸
Approved in United States as IL13Rα2-specific CAR T cells for:
  • Recurrent or refractory IL13Rα2-positive brain tumors in children

Find a Clinic Near You

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+

Food and Drug Administration (FDA)

Collaborator

Trials
184
Recruited
1,553,000+

Findings from Research

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.
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]
Integrating co-stimulatory signaling domains into a tumor-targeting CAR (IL13-CD28-41BBzeta) significantly enhances the activation and sustained function of CD4+ T cells against tumors, compared to using CD3zeta activation alone.
In vivo studies showed that CD4+ T cells with the co-stimulatory CAR effectively controlled established CNS glioma xenografts in mice, highlighting the potential for improved anti-tumor responses in the tumor microenvironment.
Transgene-enforced co-stimulation of CD4+ T cells leads to enhanced and sustained anti-tumor effector functioning.Chang, L., Chang, WC., McNamara, G., et al.[2017]
The study demonstrates that second-generation IL13-BBζ CAR T cells show superior proliferation and antitumor potency against glioblastoma compared to first-generation and third-generation CAR designs, indicating enhanced efficacy in targeting the cancer antigen IL13Rα2.
IL13-BBζ CARs also exhibit improved selectivity for the intended tumor target over the unintended target IL13Rα1, which is crucial for minimizing off-tumor effects and enhancing safety in cancer therapy.
Inclusion of 4-1BB Costimulation Enhances Selectivity and Functionality of IL13Rα2-Targeted Chimeric Antigen Receptor T Cells.Starr, R., Aguilar, B., Gumber, D., et al.[2023]

References

Characterization and Functional Analysis of scFv-based Chimeric Antigen Receptors to Redirect T Cells to IL13Rα2-positive Glioma. [2018]
Transgene-enforced co-stimulation of CD4+ T cells leads to enhanced and sustained anti-tumor effector functioning. [2017]
Inclusion of 4-1BB Costimulation Enhances Selectivity and Functionality of IL13Rα2-Targeted Chimeric Antigen Receptor T Cells. [2023]
Glioblastoma-targeted CD4+ CAR T cells mediate superior antitumor activity. [2019]
Chimeric Antigen Receptor T Cells With Modified Interleukin-13 Preferentially Recognize IL13Rα2 and Suppress Malignant Glioma: A Preclinical Study. [2021]
The Influence of Chimeric Antigen Receptor Structural Domains on Clinical Outcomes and Associated Toxicities. [2021]
Transgenic Expression of IL15 Improves Antiglioma Activity of IL13Rα2-CAR T Cells but Results in Antigen Loss Variants. [2018]
Suppression of human glioma xenografts with second-generation IL13R-specific chimeric antigen receptor-modified T cells. [2021]
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