NCT03389230

Memory-Enriched T Cells in Treating Patients With Recurrent or Refractory Grade III-IV Glioma

Phase I Study of Cellular Immunotherapy Using Memory-Enriched T Cells Lentivirally Transduced to Express a HER2-Specific, Hinge-Optimized, 41BB-Costimulatory Chimeric Receptor and a Truncated CD19 for Patients With Recurrent/Refractory Malignant Glioma

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 29 (actual)
• Sponsor: City of Hope Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of memory-enriched T cells in treating patients with grade II-IV glioma that has come back (recurrent) or does not respond to treatment (refractory). Memory enriched T cells such as HER2(EQ)BBζ/CD19t+ T cells may enter and express its genes in immune cells. Immune cells can be engineered to kill glioma cells in the laboratory by inserting a piece of deoxyribonucleic acid (DNA) into the immune cells that allows them to recognize glioma cells. A vector called lentivirus is used to carry the piece of DNA into the immune cell. It is not known whether these immune cells will kill glioma tumor cells when given to patients.

Detailed description

PRIMARY OBJECTIVES: I. To assess the feasibility and safety of cellular immunotherapy utilizing ex vivo expanded autologous memory-enriched T cells that are genetically modified using a self-inactivating (SIN) lentiviral vector to express a HER2-specific, hinge-optimized, 41BB-costimulatory chimeric antigen receptor (CAR), as well as a truncated human CD19 (HER2\[EQ\]BBzeta/CD19t+) for participants with recurrent/refractory malignant glioma in one of the following ways: Arm 1 (intracavitary/intratumoral HER2(EQ)BBzeta/CD19+ T CM), Arm 2 (dual delivery \[both intracavitary/intratumoral and intraventricular\] of HER2(EQ)BBzeta/CD19+ T CM), or Arm 3 (dual delivery \[both intracavitary/intratumoral and intraventricular\] of HER2(EQ)BBzeta/CD19+ T N/MEM). II. To determine maximum tolerated dose schedule (MTD) and a recommended Phase II dosing plan (RP2D) for arm 3 (dual delivery). SECONDARY OBJECTIVES: I. To describe persistence and expansion of CAR T cells in tumor cyst fluid, peripheral blood and cerebral spinal fluid (CSF). II. To describe cytokine levels (tumor cyst fluid, peripheral blood, and CSF) over the study period. III. In research participants who receive the full schedule of 3 CAR T cell doses: IIIa. To estimate median progression free survival (PFS) rate. IIIb. To estimate disease response rates. IIIc. To estimate median overall survival (OS). IV. In research participants who continue to receive infusions after progressing: IVa. Estimate disease response. IVb. Describe CAR T cell and endogenous immune populations, as well as cytokine and microenvironment profiles (cerebral spinal fluid \[CSF\], cyst fluid, peripheral blood) considering post progression therapy(ies), if applicable. V. For study participants who undergo an additional biopsy/resection or autopsy: Va. Evaluate CAR T cell persistence in the tumor micro-environment and the location of the CAR T cells with respect to the injection. Vb. Evaluate HER2 antigen expression levels pre and post CAR T cell therapy. OUTLINE: This is a dose-escalation study of autologous HER2(EQ)BBζ/CD19t+ T cells. Participants are assigned to 1 of 3 arms. ARM I: Patients receive autologous HER2(EQ)BBzeta/CD19t+ Tcm cells via intratumoral/intracavitary catheter over 5 minutes weekly for 3 weeks. Beginning as early as 1 week later, patients may receive additional T cell infusions as long as patients remain eligible and there is product available. Patients who progress on intracavitary or intratumoral administration may move to alternative delivery routes for the optional infusions. ARM II: Patients receive autologous HER2(EQ)BBzeta/CD19t+ Tcm cells via intratumoral/intracavitary catheter and intraventricular catheter over 5 minutes weekly for 3 weeks. Beginning as early as 1 week later, patients may receive additional T cell infusions as long as patients continue to remain eligible and there is product available. Based on clinical response after the first 3 infusions, the study principal investigator may decide to continue with the optional infusions at either one or both sites (instead of requiring injections at both sites). ARM III: Patients receive autologous HER2(EQ)BBzeta/CD19t+ Tn/mem cells via intratumoral/intracavitary catheter and intraventricular catheter over 5 minutes weekly for 3 weeks. Beginning as early as 1 week later, patients may receive additional T cell infusions as long as patients continue to remain eligible and there is product available. Based on clinical response after the first 3 infusions, the study principal investigator may decide to continue with the optional infusions at either one or both sites (instead of requiring injections at both sites). After completion of study treatment, patients are followed up at 4 weeks, 3, 6, 8, 10, and 12 months, then annually for at least 15 years.

Conditions

• Glioblastoma
• Malignant Glioma
• Recurrent Glioma
• Refractory Glioma
• WHO Grade III Glioma

Interventions

Type	Name	Description
BIOLOGICAL	HER2(EQ)BBζ/CD19t+ T cells	Given via catheter
OTHER	Laboratory Biomarker Analysis	Correlative studies
PROCEDURE	Leukapheresis	Undergo leukapheresis

Timeline

• Start date: 2018-08-14
• Primary completion: 2026-12-29
• Completion: 2026-12-29
• First posted: 2018-01-03
• Last updated: 2026-02-04

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study