NCT03283631

Intracerebral EGFR-vIII CAR-T Cells for Recurrent GBM

INTERCEPT: INTracerebral EGFR-vIII Chimeric Antigen Receptor Gene-Modified T CElls for PaTients With Recurrent GBM

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Gary Archer Ph.D. · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

The goal of this protocol is to transfer autologous peripheral blood mononuclear cells (PBMCs) transduced with genes encoding a chimeric antigen receptor (CAR) that recognizes epidermal growth factor receptor variant III (EGFRvIII) tumor-specific antigen into patients with recurrent glioblastoma (GBM) following stereotactic radiosurgery (SRS). The CAR used is targeted to a tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, which is expressed on a subset of patients. Normal PBMCs derived from patients with GBM are genetically engineered with a viral vector encoding the CAR and infused directly into the patient's tumor with the aim of mediating regression of their tumors. Despite our CAR being targeted to a tumor specific antigen, given the prior toxicity using CARs that were not targeted to tumor-specific antigens, the investigators elected to begin with very low doses of cells. Enrollment on this study was suspended in April 2020 while an amendment to reduce the anticipated number of participants was under review and approved. The decision to terminate the study was made in January, 2021 to shift toward the next iteration of a related CAR T cell trial.

Detailed description

Patients with evidence of radiographic recurrence who expressed EGFRvIII on their original tumor diagnosis had autologous PBMCs harvested by leukapheresis. These autologous PBMCs were transduced with a retrovirus containing the sequences for the EGFRvIII CAR and sent to the Duke Radiopharmacy for radiolabeling with 111Indium (111In). Within 2-3 weeks of leukapheresis, on Day -4 to -2, patients had a BrainLab MRI to prepare for biopsy and catheter placement. On Day -1, the patient underwent standard of care (SOC) stereotactic biopsy under local anesthesia to confirm tumor recurrence. At the time of biopsy, prior to catheter insertion and administration of study drug, the presence of recurrent tumor was confirmed by histopathology. If tumor recurrence was confirmed, a catheter was placed intratumorally for delivery of EGFRvIII-CARs by Convection Enhanced Delivery (CED). SRS will took place on Day 0 (+1 day) and 111In-labeled EGFRvIII-CARs were infused on the same day over a 6 to 6.5 hour period immediately after SRS. On days 1 and 2 after 111In-labeled EGFRvIII-CAR infusion, whole planar imaging followed by Single-Photon Emission Computed Tomography (SPECT) Computed Tomography (CT) imaging assessed the intracerebral and systemic localization of the 111In-labeled EGFRvIII-CARs that described the distribution of EGFRvIII-CARs within the brain and systemically. This protocol was designed to determine the maximum tolerated dose (MTD) of a novel, tumor-specific treatment with autologous EGFRvIII-CARs. The proposed starting dose was 2.5 x 10\^8 of 111In-labeled cells in 3 milliliters (mL). The infusion flow rate was fixed at 0.5 mL/hr. Enrollment on this study was suspended in April 2020 while an amendment to reduce the anticipated number of participants was under review and approved. Upon approval of this amendment, the enrollment suspension remained due to a change in access to necessary equipment for CAR manufacturing. The decision to terminate the study was made in January, 2021 to shift toward the next iteration of a related CAR T cell trial. The knowledge gained from this study experience is directing our next CAR T-cell platform and will be used to secure additional funding.

Conditions

• Recurrent Glioblastoma
• Recurrent Gliosarcoma

Interventions

Type	Name	Description
BIOLOGICAL	EGFRvIII-CARs	Gamma-retroviral MSGV1 139 scFv EGFRvIII CAR gene-modified T cells

Timeline

• Start date: 2018-05-30
• Primary completion: 2019-09-19
• Completion: 2020-06-30
• First posted: 2017-09-14
• Last updated: 2021-04-05

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study