Trials / Active Not Recruiting

Active Not RecruitingNCT02208362

Genetically Modified T-cells in Treating Patients With Recurrent or Refractory Malignant Glioma

Phase I Study of Cellular ImmunoTx Using Memory Enriched T Cells Lentivirally Transduced to Express an IL13Rα2-Specific, Hinge-Optimized, 41BB-Costimulatory Chimeric Receptor and a Truncated CD19 for Pts With Rec/Ref MaligGlioma

Status: Active Not Recruiting
Phase: Phase 1
Study type: Interventional
Enrollment: 65 (actual)

Sponsor: City of Hope Medical Center · Academic / Other
Sex: All
Age: 12 Years – 75 Years
Healthy volunteers: Not accepted

Summary

This phase I trial studies the side effects and best dose of genetically modified T-cell immunotherapy in treating patients with malignant glioma that has come back (recurrent) or has not responded to therapy (refractory). A T cell is a type of immune cell that can recognize and kill abnormal cells in the body. T cells are taken from the patient's blood and a modified gene is placed into them in the laboratory and this may help them recognize and kill glioma cells. Genetically modified T-cells may also help the body build an immune response against the tumor cells.

Detailed description

PRIMARY OBJECTIVES: I. Assess the feasibility and safety of cellular immunotherapy utilizing ex vivo expanded autologous memory-enriched T cells (Arms 1, 2, 3, or 4 = Tcm or Arm 5 = Tn/mem) that are genetically modified using a self-inactivating (SIN) lentiviral vector to express an interleukin 13 receptor alpha 2 (IL13Ra2)-specific, hinge-optimized, 41BB-costimulatory chimeric antigen receptor (CAR), as well as a truncated CD19 (CD19t) for participants with recurrent/refractory malignant glioma in one of the following ways: (1) directly into the tumor (intratumoral), (2) into the tumor cavity (intracavitary), (3) into the lateral ventricles (intraventricular), or (4) into both the tumor/tumor cavity (intratumoral) and into the lateral ventricles (intraventricular) (dual delivery). II. Determine maximum tolerated dose schedule (MTD)/maximum feasible dose schedule (MFD) and a recommended phase II dosing plan (RP2D) for each arm based on dose limiting toxicities (DLTs) and the full toxicity profile. SECONDARY OBJECTIVES: I. In research participants who receive the full schedule of three CAR+ T cell doses: * Estimate disease response rates, * Estimate median overall survival, and * Estimate the mean change from baseline in quality of life using the EORTC QLQ-C30 during and post treatment; II. Describe cytokine levels (tumor cavity fluid, CSF, peripheral blood) over the study period. III. Describe CAR T cell and endogenous immune populations (CSF, tumor cavity fluid, peripheral blood) over the study period; and IV. Identify tumor and tumor micro-environment markers associated with response to CAR T cells. EXPLORATORY OBJECTIVES: I. Assess the timing and extent of brain inflammation following CAR T cell administration; II. Evaluate CAR T cell product characteristics; and III. For research participants who undergo a second resection or autopsy: * Evaluate CAR T cell persistence in the tumor micro-environment and the location of the CAR T cells with respect to the injection, and * Evaluate IL13Rα2 antigen expression levels pre and post CAR T cell therapy. OUTLINE: This is a dose-escalation study. Research subjects will receive an initial low dose (cycle 1) followed by 2 additional infusions at a higher cell dose (cycles 2 and 3) of autologous IL13Ra2-CAR/CD19t+ Tcm or Tn/mem, potentially followed by additional cycles at up to the highest tolerated cell dose (cycles 4+). CAR T cells will be administered in one of four ways: ARM 1: (Intratumoral delivery a/f biopsy): Patients receive IL13Ra2-CAR/CD19t+ Tcm directly into the tumor via intratumoral (ICTb) catheter. Patients who progress on intratumoral administration may move to intraventricular catheter for the optional infusions. ARM 2: (Intratumoral delivery a/f biopsy/Intracavitary a/f resection): Patients receive IL13Ra2-CAR/CD19t+ Tcm directly into the tumor via intratumoral (ICTb) catheter, or into the tumor resection cavity via intracavitary (ICTr) catheter. Patients who progress on intratumoral/intracavitary administration may move to intraventricular catheter for the optional infusions. ARM 3: (Intraventricular delivery): Patients receive IL13Ra2-CAR/CD19t+ Tcm via intraventricular (ICV) catheter. ARM 4: (Dual delivery): Patients receive IL13Ra2-CAR/CD19t+ Tcm via ICTb/r catheter and ICV catheter. 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 5: (Dual delivery): Patients receive IL13Ra2-CAR/CD19t+ Tn/mem via ICTb/r catheter and ICV catheter. 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). CAR T cells will be administered at one of three dose schedules: * Dose Schedule 1: Cycle 1 - 2x106 CAR T cells, Cycle 2 \& 3 - 10x106 CAR T cells, Total dose - 22x106 CAR T cells; Optional cycles ≤10x106 CAR T cells * Dose Schedule 2: Cycle 1 - 10x106 CAR T cells, Cycle 2 \& 3 - 50x106 CAR T cells, Total dose - 110x106 CAR T cells; Optional cycles ≤50x106 CAR T cells * Dose Schedule 3: Cycle 1 - 20x106 CAR T cells, Cycle 2 \& 3 - 100x106 CAR T cells, Total dose - 220x106 CAR T cells; Optional cycles ≤100x106 CAR T cells After completion of the study treatment, patients are followed up at 4 weeks, 3, 6, 8, 10, and 12 months, and then yearly for 15 years.

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	Arm 1: IL13Ra2-specific CAR Tcm cells	Given via intratumoral catheter
BIOLOGICAL	Arm 2: IL13Ra2-specific CAR Tcm cells	Given via intratumoral/intracavitary catheter
BIOLOGICAL	Arm 3: IL13Ra2-specific CAR Tcm cells	Given via intraventricular catheter
BIOLOGICAL	Arm 4: IL13Ra2-specific CAR Tcm cells	Given via intratumoral or intracavitary, and via intraventricular catheter
BIOLOGICAL	Arm 5: IL13Ra2-specific CAR Tn/mem cells	Given via intratumoral or intracavitary, and via intraventricular catheter
OTHER	Laboratory Biomarker Analysis	Correlative studies
PROCEDURE	Magnetic Resonance Imaging	Correlative studies
PROCEDURE	Magnetic Resonance Spectroscopic Imaging	Correlative studies
OTHER	Quality-of-Life Assessment	Ancillary studies

Timeline

Start date: 2015-05-18
Primary completion: 2021-02-08
Completion: 2026-06-08
First posted: 2014-08-05
Last updated: 2025-09-03
Results posted: 2024-10-30

Locations

1 site across 1 country: United States

Source: ClinicalTrials.gov record NCT02208362. Inclusion in this directory is not an endorsement.