NCT04385173

Pilot Study of B7-H3 CAR-T in Treating Patients With Recurrent and Refractory Glioblastoma

A Pilot Study of Chimeric Antigen Receptor (CAR) T Cells Targeting B7-H3 Antigen in Treating Patients With Recurrent and Refractory Glioblastoma

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 12 (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 pilot phase I study to evaluate the safety and efficacy on B7-H3 CAR-T in between Temozolomide cycles 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 to the historical Temozolomide data * To access the pharmacokinetics and pharmacodynamics of B7-H3 CAR-T in between Temozolomide cycles Design 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 in the cycle 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.

Conditions

• Recurrent Glioblastoma
• Refractory Glioblastoma

Interventions

Type	Name	Description
DRUG	B7-H3 CAR-T	The B7-H3 CAR-T will be administrated via intratumoral or Intracerebroventricular injection through an Ommaya catheter in between Temozolomide cycles. Temozolomide will be stopped during the infusion of B7-H3 CAR-T
DRUG	Temozolomide	Temozolomide will be given to patients orally every 5 days with 23 days interval. The initial dose is 150 mg/m2 on the first day and 200 mg/m2 for the rest if no toxicity is seen. If 200 mg/m2 is toxic, the drug will return to 150 mg/m2 or will be stopped.

Timeline

• Start date: 2022-12-01
• Primary completion: 2024-03-01
• Completion: 2024-05-01
• First posted: 2020-05-12
• Last updated: 2022-12-28

Locations

1 site across 1 country: China