EGFRBi-Armed Autologous T Cells in Treating Patients With Recurrent or Refractory Glioblastoma

Adult Gliosarcoma Clinical Trial

Official title: Targeting Recurrent Glioblastoma With Anti-CD3 x Anti-EGFR Bispecific Antibody Armed T Cells: A Phase I/II Study

Status Withdrawn

Clinical Trial Summary

This phase I/II trial studies the side effects and best dose of epidermal growth factor receptor bispecific antibody (EGFRBi)-armed autologous T cells and how well it works in treating patients with glioblastoma that have come back or does not respond to treatment. EGFRBi-armed autologous T cells coated with antibodies (proteins used by the immune system to target and kill foreign objects such as cancer cells) may have great ability to seek out, attach to, and destroy glioblastoma cells.

Clinical Trial Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) for 8 intrathecal (IT) injections (via lumbar puncture) of anti-cluster of differentiation (CD)3 × anti-EGFRBi armed activated T cells (aATC) (EGFRBi-armed autologous T cells) given twice per week for 4 weeks in a standard 3+3 dose escalation schema with 0.10, 0.50 and 1.00 × 10^9 EGFRBi-aATC per IT injection for a total of 0.8, 4.0, and 8.0 × 10^9 cells, respectively. (Phase I) II. To explore efficacy and confirm the toxicity profile of EGFRBi-aATC. (Phase II)

SECONDARY OBJECTIVES:

I. Measure immune responses in participants of the phase I/II trial by sequential monitoring of phenotype, interferon gamma (IFN-g) enzyme-linked immunoSpots (EliSpots), anti-glioblastoma (GBM) cytotoxicity of peripheral blood mononuclear cell (PBMC) (direct cytotoxicity against GBM cells) directed at GBM cell lines, T-helper 1 (Th1)/T-helper 2 (Th2) serum cytokine patterns, and anti-glioma antibodies in the cerebrospinal fluid (CSF)/serum during the "vaccinate and consolidate" process.

II. Assess survival and persistence of aATC in the CSF, and trafficking of IT-injected aATC out of the CSF into the bloodstream.

III. Image patients' brain with magnetic resonance imaging (MRI) (performed clinically in 2-month intervals; includes standard structural sequences and perfusion imaging) and alpha-[11C]methyl-L-tryptophan (AMT) positron emission tomography (PET) scan (under Wayne State University [WSU] Internal Review Board [IRB]/Karmanos Cancer Institute [KCI]-approved research protocol) before and after the aATC treatment regimen.

OUTLINE: This is a phase I dose-escalation study followed by a phase II study.

PHASE I: Patients receive EGFRBi-armed autologous T cells IT twice weekly for 4 weeks.

PHASE II: Patients receive EGFRBi-armed autologous T cells* IT twice weekly for 4 weeks and then intravenously (IV) over 15-30 minutes twice weekly for 2 weeks.

*NOTE: Six selected patients receive EGFRBi-armed autologous T cells IV on day -3, -2, or -1 prior to first IT infusion.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months thereafter. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Adult Brain Glioblastoma
• Adult Gliosarcoma
• Brain Neoplasms
• Glioblastoma
• Gliosarcoma
• Recurrent Brain Neoplasm

• NCT number: NCT02521090
• Study type: Interventional
• Source: Barbara Ann Karmanos Cancer Institute
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• Start date: August 2015