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

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.