This phase I trial investigates the side effects of chemotherapy and cellular immunotherapy in treating children with IL13Ralpha2 positive brain tumors that have come back after a period of improvement (recurrent) or do not respond to treatment (refractory). Cellular immunotherapy (IL13(EQ)BBzeta/CD19t+ T cells) are brain-tumor specific cells that may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as as cyclophosphamide and fludarabine, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Many patients with brain tumor respond to treatment, but then the tumor starts to grow again. Giving chemotherapy in combination with cellular immunotherapy may kill more tumor cells and improve the outcome of treatment.
Documented informed consent of the participant and/or legally authorized representative.
Assent, when appropriate, will be obtained per institutional guidelines
Agreement to allow the use of archival tissue from diagnostic tumor biopsies
Karnofsky Performance Status (KPS) >= 60% except for loss of mobility due to disease involvement; e.g., confinement to a wheelchair due to spinal cord compression
Pulmonary: Research participant requires supplemental oxygen to keep saturation greater than 95% and the situation is not expected to resolve within 2 weeks
Cardiac: Research participant requires pressor support and/or has symptomatic cardiac arrhythmias
Renal: Research participant requires dialysis
Neurologic: Research participant has uncontrolled seizure activity and/or clinically evident progressive encephalopathy
Single group
Cyclophosphamide
DrugGiven IV
Fludarabine
DrugGiven IV
IL13Ralpha2-specific Hinge-optimized 41BB-co-stimulatory CAR Truncated CD19-expressing Autologous T-Lymphocytes
Biological/VaccineGiven intraventricularly
Incidence of adverse events
Will assess the incidence of grade 3 toxicities, dose limiting toxicities, and all other toxicities. Toxicity and adverse events will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0 and the revised cytokine release syndrome (CRS) grading system. Symptoms and toxicities will be evaluated by physical exam and blood chemistry/hematology results and adverse event reporting. Rate and associated 90% Clopper and Pearson binomial confidence limits (90% CI) will be estimated for participants experiencing dose limiting toxicities. Tables will be created to summarize all toxicities and side effects by time post treatment, organ, severity and disease subgroup.
Persistence and expansion of CAR T cells
Will assess CAR T cells detected in peripheral blood and cerebrospinal fluid (CSF). Descriptive statistical and graphical methods will be used to describe persistence and expansion of the CAR T cells (peripheral blood \[PB\] and CSF).
Peripheral blood and CSF cytokine levels
Descriptive statistical and graphical methods will be used to describe cytokine levels (PB and CSF).
Peripheral blood and CSF immune cell characterization
Progression free survival
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City of Hope Medical Center
Lead sponsor
National Cancer Institute (NCI)
Collaborator
