NCT05063682

The Efficacy and Safety of Brain-targeting Immune Cells (EGFRvIII-CAR T Cells) in Treating Patients With Leptomeningeal Disease From Glioblastoma. Administering Patients EGFRvIII -CAR T Cells May Help to Recognize and Destroy Brain Tumor Cells in Patients

A Phase 1 Study to Evaluate EGFRvIII -Targeted Chimeric Antigen Receptor (CAR) T Cells for Adult Patients With Leptomeningeal Glioblastoma

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: Chembrain LTD · Industry
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial investigates the efficacy and safety of brain-targeting epidermal growth factor receptor chimeric antigen receptor immune cells (EGFRvIII-CAR T cells) in treating patients with leptomeningeal disease from glioblastoma. T cells are part of the immune system and help the body fight malignant tumours. Immune cells can be genetically modified to destroy brain tumor cells in the laboratory. EGFRvIII -CAR T cells are brain tumor specific and can enter and express its genes in immune cells. Administering patients EGFRvIII -CAR T cells may help to recognize and destroy brain tumor cells in patients with leptomeningeal disease from glioblastoma.

Detailed description

PRIMARY OBJECTIVES: 1. Examine and describe the safety and feasibility of EGFRvIII-specific hinge-optimized CD3 ζ-stimulatory/41BB-co-stimulatory Chimeric Antigen Receptor autologous T-lymphocytes (EGFRvIII -CAR T cells) through intracerebroventricular (ICV) delivery as adjuvant therapy in participants with EGFRvIII+ leptomeningeal disease from glioblastoma. 2. Determine the activity of EGFRvIII -CAR T cells based on survival rate at 12 months for both arms. SECONDARY OBJECTIVES: 1. Describe persistence, expansion and phenotype of endogenous and EGFRvIII -CAR T cells in peripheral blood (PB), tumor cyst fluid (TCF) and cerebral spinal fluid (CSF) at applicable time points 2. Describe cytokine levels in PB, TCF, and CSF at applicable time points 3. Estimate the rate of disease response by Response Assessment in Neuro-Oncology Leptomeningeal Metastases (RANO LM) criteria 4. Estimate rate of progression free survival at 6 months. Estimate rate of overall survival (OS) at 12 months by study arm. 5. Estimate time to next treatment 6. Evaluate EGFRvIII -CAR T cell persistence in the tumor tissue and the location of the EGFRvIII -CAR T cells with respect to the infusion site. 7. Evaluate biomarkers and cytokine levels OUTLINE: Patients receive EGFRvIII -CAR T cells intracerebroventricular over 15 minutes on day 1. Patients may receive additional cycles based on the persistence of the cells. The patients are followed extensively according to the clinical pharmacology sampling plan; on days 1-30, months 2-12, and three times per year up to 10 years based on response

Conditions

• Glioblastoma
• Glioblastoma Multiforme
• Glioma, Malignant

Interventions

Type	Name	Description
BIOLOGICAL	EGFRvIII-specific hinge-optimized CD3 ζ-stimulatory/41BB-co-stimulatory Chimeric Antigen Receptor autologous T-lymphocytes	ICV administration

Timeline

• Start date: 2020-05-15
• Primary completion: 2023-10-01
• Completion: 2023-10-01
• First posted: 2021-10-01
• Last updated: 2021-10-01

Locations

3 sites across 2 countries: Finland, India