NCT04077866

B7-H3 CAR-T for Recurrent or Refractory Glioblastoma

B7-H3-Targeted Chimeric Antigen Receptor (CAR) T Cells in Treating Patients With Recurrent or Refractory Glioblastoma

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a randomized, parallel-arm, phase I/II study to evaluate the safety and efficacy of B7-H3 CAR-T in between Temozolomide cycles comparing to Temozolomide alone in treating patients with glioblastoma that has come back or does not respond to the standard treatment. The antigen B7-H3 is highly expressed in glioblastoma of a subset of patients. B7-H3 CAR-T, made from isolated patient peripheral blood mononuclear cells, can specifically attack patient glioblastoma cells that expressing B7-H3.

Detailed description

Background * B7-H3 is expressed in 70% of patients with glioblastoma * B7-H3 is not expressed in normal tissues especially not in central nervous system. Therefore, it is an attractive GBM target for CAR-T therapy * The investigators constructed a retroviral vector encoding a chimeric antigen receptor (CAR) targeting B7-H3, which can mediate CAR transfer into patient T cells with high efficiency. Objectives * To evaluate the safety and tolerability intratumoral/intracerebroventricular injection of B7-H3 CAR-T when used in between Temozolomide cycles * To compare the overall survival (OS) and progression-free survival (PFS) of R/R GBM patients treated with B7-H3 CAR-T in between Temozolomide cycles vs Temozolomide alone * To access the pharmacokinetics and pharmacodynamics of B7-H3 CAR-T in between Temozolomide cycles Design * Experimental group: Patients autologous T cells are activated and transduced with retrovirus containing B7-H3 CAR. CAR-T cells are expanded ex vivo and infused back to patients via intratumoral or intracerebroventricular injection through an Ommaya catheter. 3 injections of CAR-T are planned at two different doses with 1-2 weeks intervals. The CAR-T injections occur in between Temozolomide (TMZ) cycles. Temozolomide treatment during the cycles of CAR-T injections will be stopped and resumed next cycle. Patients may receive additional CAR-T cycles at the discretion of the principal investigator and oncologist. * Control group: Patients will receive regular cycles of Temozolomide treatment with 5 days of treatment and 23 days of interval.

Conditions

• Recurrent Glioblastoma
• Refractory Glioblastoma

Interventions

Type	Name	Description
DRUG	Temozolomide	Temozolomide is an FDA-approved drug that is given to patients
BIOLOGICAL	B7-H3 CAR-T	B7-H3-targeting CAR-T cells derived from patient own peripheral blood mononuclear cells will be given to patients via intracerebral injection though an Ommaya catheter

Timeline

• Start date: 2023-06-01
• Primary completion: 2025-06-01
• Completion: 2025-08-01
• First posted: 2019-09-04
• Last updated: 2022-12-28

Locations

3 sites across 1 country: China