CAR T-Cell Therapy for Brain Cancer
Recruiting in Palo Alto (17 mi)
Overseen ByReena Thomas, MD, PhD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Crystal Mackall, MD
No Placebo Group
Trial Summary
What is the purpose of this trial?This is an open label, non-randomized, single site Phase I study to test the manufacturing feasibility and safety of locoregional (LR) administration of B7-H3CART into the central nervous system of adult subjects with recurrent IDH wild-type GBM using a standard 3+3 dose escalation design.
Will I have to stop taking my current medications?
The trial protocol does not specify if you need to stop taking your current medications. However, you must limit steroid use to 4 mg of decadron daily and meet certain timing requirements after previous cancer treatments. It's best to discuss your specific medications with the trial team.
What data supports the effectiveness of the treatment B7-H3CART for brain cancer?
Research shows that B7-H3CART, a type of CAR T-cell therapy, has shown promise in treating glioblastoma (a type of brain cancer) by targeting the B7-H3 protein, which is often found in high levels in these tumors. Studies have demonstrated that this treatment can extend survival in animal models and has potential for use in pediatric brain tumors.
12345Is CAR T-Cell Therapy targeting B7-H3 safe for brain cancer patients?
While CAR T-Cell Therapy targeting B7-H3 shows promise for treating brain cancer, there are concerns about severe side effects, including neurotoxicity (nerve damage) that can lead to serious conditions like encephalopathy (brain disease) and cerebral edema (brain swelling). The safety of this therapy is still being studied, and its effects can vary.
12367What makes the B7-H3CART treatment unique for brain cancer?
B7-H3CART is a novel treatment that uses specially engineered immune cells (CAR T-cells) to target a protein called B7-H3, which is often found on brain cancer cells like glioblastoma. This approach is unique because it aims to directly attack cancer cells by recognizing this specific protein, potentially offering a new option for a condition with limited effective treatments.
12345Eligibility Criteria
Adults aged 18-75 with recurrent high-grade glioblastoma, IDH wild-type, who have completed standard therapy and show tumor progression. They must be stable on low-dose steroids, have good organ function and performance status, not pregnant or breastfeeding, willing to use contraception, able to follow study procedures at Stanford Health Care.Participant Groups
The trial is testing B7-H3CART cells delivered directly into the brain of patients with recurrent glioblastoma. It's a Phase I study focusing on safety and how well the treatment can be made using a '3+3 dose escalation' method where doses are increased slowly in small groups.
2Treatment groups
Experimental Treatment
Group I: Dose escalationExperimental Treatment1 Intervention
All subjects will be assigned to a dose level. Does escalation will proceed sequentially via a standard 3+3 dose escalation design in subjects who receive at least one infusion of B7-H3CART. Each dose level will include 3 to 6 subjects, starting at Dose Level 1. If Dose Level 1 is considered too toxic, the dose may be de-escalated to Dose Level -1. If Dose Level 4 is completed with no dose limiting toxicity (DLT) in six subjects, a maximum tolerated dose (MTD) may not be determined, and Dose Level 4 will instead be the maximum administered dose (MAD). T
Group II: Dose ExpansionExperimental Treatment1 Intervention
After Maximum Tolerated Dose (MTD)/Recommended Phase 2 Dose (RP2D) is established, a total of 12 evaluable subjects (including the 6 subjects infused during the dose escalation phase) will be enrolled at the RP2D to further explore safety of repeat administrations at MTD/RP2D and conduct a preliminary assessment of benefit.
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Stanford Cancer InstitutePalo Alto, CA
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Who is running the clinical trial?
Crystal Mackall, MDLead Sponsor
California Institute for Regenerative Medicine (CIRM)Collaborator
References
B7-H3 as a Novel CAR-T Therapeutic Target for Glioblastoma. [2020]Glioblastoma (GBM) remains one of the most malignant primary tumors in adults, with a 5-year survival rate less than 10% because of lacking effective treatment. Here, we aimed to explore whether B7-H3 could serve as a novel therapeutic target for GBM in chimeric antigen receptor (CAR) T cell therapy. In this study, a CAR targeting B7-H3 was constructed and transduced into T cells by lentivirus. Antitumor effects of B7-H3-specific CAR-T cells were assessed with primary and GBM cell lines both in vitro and in vivo. Our results indicated that B7-H3 was positively stained in most of the clinical glioma samples, and its expression levels were correlated to the malignancy grade and poor survival in both low-grade glioma (LGG) and GBM patients. Specific antitumor functions of CAR-T cells were confirmed by cytotoxic and ELISA assay both in primary glioblastoma cells and GBM cell lines. In the orthotropic GBM models, the median survival of the CAR-T-cell-treated group was significantly longer than that of the control group. In conclusion, B7-H3 is frequently overexpressed in GBM patients and may serve as a therapeutic target in CAR-T therapy.
CAR-T cells for pediatric brain tumors: Present and future. [2021]Chimeric Antigen Receptor T (CAR-T) cells are currently approved for B cell malignancies only, in children and adults. Despite a lack of robust evidence to approve such cellular immunotherapy for pediatric solid tumors, there is a growing interest for this approach in the treatment of pediatric brain tumors. Following the identification of tumor antigens as targets, the first clinical trials demonstrated some degree of clinical and biological responses to CAR-T cells for such tumor types. Additionaly, several preclinical studies have recently identified new attractive targets and antigen combination strategies, along with a superior tumor trafficking following locoregional administration. We review here the preclinical and clinical knowledge at the basis of the current clinical development of CAR-T cells for pediatric brain tumors.
CAR T Cells Targeting B7-H3, a Pan-Cancer Antigen, Demonstrate Potent Preclinical Activity Against Pediatric Solid Tumors and Brain Tumors. [2021]Patients with relapsed pediatric solid tumors and CNS malignancies have few therapeutic options and frequently die of their disease. Chimeric antigen receptor (CAR) T cells have shown tremendous success in treating relapsed pediatric acute lymphoblastic leukemia, but this has not yet translated to treating solid tumors. This is partially due to a paucity of differentially expressed cell surface molecules on solid tumors that can be safely targeted. Here, we present B7-H3 (CD276) as a putative target for CAR T-cell therapy of pediatric solid tumors, including those arising in the central nervous system.
B7-H3-redirected chimeric antigen receptor T cells target glioblastoma and neurospheres. [2021]The dismal survival of glioblastoma (GBM) patients urgently calls for the development of new treatments. Chimeric antigen receptor T (CAR-T) cells are an attractive strategy, but preclinical and clinical studies in GBM have shown that heterogeneous expression of the antigens targeted so far causes tumor escape, highlighting the need for the identification of new targets. We explored if B7-H3 is a valuable target for CAR-T cells in GBM.
Cell-surface antigen profiling of pediatric brain tumors: B7-H3 is consistently expressed and can be targeted via local or systemic CAR T-cell delivery. [2023]Immunotherapy with chimeric antigen receptor (CAR) T cells is actively being explored for pediatric brain tumors in preclinical models and early phase clinical studies. At present, it is unclear which CAR target antigens are consistently expressed across different pediatric brain tumor types. In addition, the extent of HLA class I expression is unknown, which is critical for tumor recognition by conventional αβTCR T cells.
Clinical Predictors of Neurotoxicity After Chimeric Antigen Receptor T-Cell Therapy. [2021]Chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory hematologic malignant neoplasm causes severe neurologic adverse events ranging from encephalopathy and aphasia to cerebral edema and death. The cause of neurotoxicity is incompletely understood, and its unpredictability is a reason for prolonged hospitalization after CAR T-cell infusion.
Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy for Glioblastoma: A Systemic Review and Meta-Analysis. [2023]Chimeric antigen receptor (CAR) T-cell therapy is a promising treatment option for patients with refractory hematological malignancies. However, its efficacy in glioblastoma remains unclear. Here, we performed a systematic review to summarize the safety and efficacy of CAR T-cell therapy in glioblastoma.