CAR T-Cell Therapy + Immunotherapy for Glioblastoma
Trial Summary
Do I have to stop taking my current medications for this trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you are steroid-dependent, requiring more than 6 mg of dexamethasone per day. It's best to discuss your current medications with the study team.
What data supports the idea that CAR T-Cell Therapy + Immunotherapy for Glioblastoma is an effective treatment?
The available research shows that CAR T-Cell Therapy targeting IL13Rα2 is promising for treating glioblastoma. In one study, mice treated with IL13Rα2-specific CAR T cells showed significant survival advantages compared to those that did not receive the treatment. Another study demonstrated that these CAR T cells, when modified with IL15, had greater antiglioma activity and persisted longer, leading to better outcomes. Additionally, a case report highlighted that direct delivery of CAR T cells into the cerebrospinal fluid completely eliminated a patient's brain and spinal tumors for 7.5 months, allowing the patient to resume normal activities. These findings suggest that this treatment can be more effective than traditional therapies like surgery, radiation, and chemotherapy, which often result in frequent recurrences.12345
What safety data exists for CAR T-Cell Therapy and Immunotherapy for Glioblastoma?
The safety data for CAR T-Cell Therapy targeting IL13Rα2 in glioblastoma includes several findings: IL13Rα2-specific CAR T cells have shown no cross-reactivity to IL13Rα1, which is important for minimizing off-target effects. Second-generation CARs with 4-1BB costimulation have demonstrated superior selectivity and antitumor potency, reducing off-target reactivity. CD4+ CAR T cells have shown superior long-term antitumor activity compared to CD8+ CAR T cells, indicating a potential safety advantage in maintaining effector function. Additionally, tandem CAR T cells targeting both HER2 and IL13Rα2 have shown enhanced antitumor efficacy and reduced antigen escape, suggesting improved safety and effectiveness. Overall, these studies indicate promising safety profiles for IL13Rα2-targeted CAR T-cell therapies in glioblastoma treatment.12467
Is the treatment IL13Ralpha2 CAR T cells a promising treatment for glioblastoma?
Yes, IL13Ralpha2 CAR T cells are a promising treatment for glioblastoma. They specifically target cancer cells without affecting normal brain cells, show strong anti-tumor activity, and can improve survival. They also help activate the body's own immune system to fight the tumor, making them a powerful option for treating this type of brain cancer.12368
What is the purpose of this trial?
This phase I trial studies the side effects and how well IL13Ralpha2-CAR T cells work when given alone or together with nivolumab and ipilimumab in treating patients with glioblastoma that has come back (recurrent) or does not respond to treatment (refractory). Biological therapies, such as IL13Ralpha2-CAR T cells, use substances made from living organisms that may attack specific glioma cells and stop them from growing or kill them. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. It is not yet known whether giving IL13Ralpha2-CAR T cells and nivolumab together may work better in treating patients with glioblastoma.
Research Team
Behnam Badie
Principal Investigator
City of Hope Medical Center
Eligibility Criteria
This trial is for adults over 18 with grade IV glioblastoma (GBM) or those whose lower-grade glioma has progressed to GBM after standard treatment. Participants must have a life expectancy of at least 4 weeks, be able to use birth control, and not require high doses of steroids. They can't join if they've had certain heart issues without clearance, uncontrolled seizures, active infections needing antibiotics, or are pregnant/breastfeeding.Inclusion Criteria
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Neoadjuvant Therapy
Patients receive nivolumab and ipilimumab as neoadjuvant therapy to assess safety and feasibility
Adjuvant Therapy
Patients receive IL13Ralpha2 CAR T cells and nivolumab, with treatment repeating weekly for up to 4 cycles
Follow-up
Participants are monitored for safety and effectiveness after treatment
Treatment Details
Interventions
- IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells
- Ipilimumab
- Nivolumab
IL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells is already approved in United States for the following indications:
- Stage IIIC or IV melanoma
- Metastatic solid tumors
Find a Clinic Near You
Who Is Running the Clinical Trial?
City of Hope Medical Center
Lead Sponsor
National Cancer Institute (NCI)
Collaborator