This phase Ib trial tests the safety, side effects and effectiveness of giving chimeric antigen T cell (CART)-epidermal growth factor receptor (EGFR)-interleukin-13 receptor alpha 2 (IL13Ra2) cells with lymphodepleting chemotherapy, fludarabine and cyclophosphamide, and prior to surgical resection in treating patients with wild-type EGFR-amplified, IDH-wildtype glioblastoma that has come back after a period of improvement (recurrent). CAR T-cell therapy is a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory so they will attack tumor cells. T cells are taken from a patient’s blood. Then the gene for a special receptor that binds to a certain protein, such as EGFR, and IL13Ralpha2, on the patient’s tumor cells is added to the T cells in the laboratory. The special receptor is called a CAR. Large numbers of the CAR T cells are grown in the laboratory and given to the patient by infusion for treatment of certain cancers. Fludarabine blocks cells from making deoxyribonucleic acid (DNA) and may kill tumor cells. It is a type of purine antagonist and a type of ribonucleotide reductase inhibitor. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell’s DNA and may kill tumor cells. It may also lower the body’s immune response. Lymphodepleting chemotherapy with fludarabine and cyclophosphamide may help the CART-EGFR-IL13Ra2 cells grow and survive in the body. Tumor resection is a surgical procedure in which tumor tissue is removed. Giving CART-EGFR-IL13Ralpha2 cells with lymphodepleting chemotherapy, fludarabine and cyclophosphamide, or prior to surgical resection may be safe, tolerable, and/or effective in treating patients with wild-type EGFR amplified, IDH-wildtype glioblastoma.
Additional locations may be listed on ClinicalTrials.gov for NCT07209241.
Locations matching your search criteria
United States
Pennsylvania
Philadelphia
University of Pennsylvania/Abramson Cancer CenterStatus: Active
Contact: Stephen Joseph Bagley
Phone: 215-615-1594
PRIMARY OBJECTIVE:
I. Evaluate the safety of different approaches for autologous anti-EGFR/anti-IL13Ralpha2 CAR T-cells (CART-EGFR-IL13Ra2) dosing.
SECONDARY OBJECTIVES:
I. Evaluate the feasibility of different approaches for CART-EGFR-IL13Ra2 dosing.
II. Describe the preliminary efficacy of different approaches for CART-EGFR-IL13Ra2 dosing.
EXPLORATORY OBJECTIVES:
I. Characterize CART-EGFR-IL13Ra2 cell pharmacokinetic profile and bioactivity in the cerebrospinal fluid (CSF), blood and tumor tissue.
II. Measure CART-EGFR-IL13Ra2 trafficking to tumor.
III. Evaluate correlative measures of CART-EGFR-IL13Ra2 cell activity and its association with efficacy measures.
OUTLINE: Patients are sequentially assigned to 1 of 3 arms according to their planned treatment date.
ARM A: Patients undergo CSF-ventricular reservoir placement and leukapheresis. Patients receive lymphodepletion with fludarabine intravenously (IV) and cyclophosphamide IV for 3 days. Starting 3 days after last dose of lymphodepleting therapy, patients receive CART-EGFR-IL13Ra2 cells via intracerebrovascular (ICV) injection on day 0. Patients who demonstrate clinical benefit after initial treatment may be eligible to receive retreatment per physician-investigator discretion. Patients receiving retreatment may repeat lymphodepleting chemotherapy, to be completed 3 days prior to retreatment dose, at the discretion of the physician-investigator. Patients also undergo echocardiography (ECHO) or multigated acquisition scan (MUGA), and chest x-ray prior to treatment and CSF and blood sample collection and magnetic resonance imaging (MRI) of the brain throughout the study.
ARM B: Patients undergo CSF-ventricular reservoir placement and leukapheresis. Patients receive lymphodepletion with fludarabine IV and cyclophosphamide IV for 3 days. Starting 3 days after last dose of lymphodepleting therapy, patients receive CART-EGFR-IL13Ra2 cells via ICV injection on days 0 and 14. Patients who demonstrate clinical benefit after initial treatment may be eligible to receive retreatment per physician-investigator discretion. Patients receiving retreatment may repeat lymphodepleting chemotherapy, to be completed 3 days prior to retreatment dose, at the discretion of the physician-investigator. Patients also undergo ECHO or MUGA, and chest x-ray prior to treatment and CSF and blood sample collection and MRI of the brain throughout the study.
ARM C: Patients undergo CSF-ventricular reservoir placement during days -13 to -2 and also undergo leukapheresis. Patients receive CART-EGFR-IL13Ra2 cells ICV injection on day 0 and undergo routine surgical tumor resection between day 5 and day 10. Patients who demonstrate clinical benefit after initial treatment may be eligible to receive retreatment per physician-investigator discretion. Patients receiving retreatment may receive lymphodepleting chemotherapy with fludarabine IV and cyclophosphamide IV, to be completed 3 days prior to retreatment dose, at the discretion of the physician-investigator. Patients also undergo ECHO or MUGA, and chest x-ray prior to treatment and CSF and blood sample collection and MRI of the brain throughout the study.
After completion of study treatment, patients are followed up on days 1, 4, 7, 10. 14, 21, and 28 after each treatment, on months 2, 3, 4, 5, 6, 8, 10, and 12. Patients are then followed up per long-term follow up at months 3, 6, 9, 12, 18 and 24. Patients with ongoing CAR T cell persistence are followed every 6 months from months 30-60 then yearly for years 6-15. Patients with no evidence of ongoing CAR T persistence are followed yearly on months 36- 60, and years 6-15.
Lead OrganizationUniversity of Pennsylvania/Abramson Cancer Center
Principal InvestigatorStephen Joseph Bagley
