Phase I Dose Escalation Study of Systemically Administered IL13Ra2 Chimeric Antigen Receptor (CAR) T Cells After a Nonmyeloablative Conditioning Regimen in Patients With Metastatic Melanoma and Other Solid Tumors
Anusha Kalbasi
Summary
This phase I trial studies the side effects and best dose of modified immune cells (IL13Ralpha2 CAR T cells) after a chemotherapy conditioning regimen for the treatment of patients with stage IIIC or IV melanoma or solid tumors that have spread to other places in the body (metastatic). The study agent is called IL13Ralpha2 CAR T cells. T cells are a special type of white blood cell (immune cells) that have the ability to kill tumor cells. The T cells are obtained from the patient's own blood, grown in a laboratory, and modified by adding the IL13Ralpha2 CAR gene. The IL13Ralpha2 CAR gene is inserted into T cells with a virus called a lentivirus. The lentivirus allows cells to make the IL13Ralpha2 CAR protein. This CAR has been designed to bind to a protein on the surface of tumor cells called IL13Ralpha2. This study is being done to determine the dose at which the gene-modified immune cells are safe, how long the cells stay in the body, and if the cells are able to attack the cancer.
Description
PRIMARY OBJECTIVE: I. To evaluate the safety of systemic administration of IL13Ralpha2-redirected CAR T cells, including determination of the maximum tolerated dose (MTD). SECONDARY OBJECTIVES: I. Clinical response. II. Determine the infiltration of IL13Ralpha2 CAR T cells into the tumor. III. Determine the persistence of IL13Ralpha2 CAR T cells in the peripheral blood. EXPLORATORY OBJECTIVES: I. Evaluate the induction of endogenous anti-tumor T cell responses in patients receiving IL13Ralpha2 CAR T cell therapy. II. Assess for the occurrence of cytokine release syndrome in patients rece…
Eligibility
- Age range
- 18–75 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Histologically confirmed malignancy that is considered surgically incurable with either: * Stage IIIC melanoma including locally relapsed, satellite, in-transit lesions or bulky draining node metastasis * Stage IV melanoma including patients with known brain metastases * Other metastatic, non-central nervous system (CNS) solid tumor relapsed or refractory after all standard-of-care systemic therapies for which the patient is eligible * Confirmed IL13Ralpha2 tumor expression by immunohistochemistry (immunohistochemical assay \[IHA\] H-Score \>= 50 in at least 10% o…
Interventions
- ProcedureBiopsy
Undergo biopsy
- ProcedureBiospecimen Collection
Undergo collection of blood samples
- ProcedureComputed Tomography
Undergo CT scan
- DrugCyclophosphamide
Given IV
- DrugFludarabine Phosphate
Given IV
- OtherFludeoxyglucose F-18
Undergo FDG-PET/CT scan
- BiologicalIL13Ralpha2-specific Hinge-optimized 4-1BB-co-stimulatory CAR/Truncated CD19-expressing Autologous TN/MEM Cells
Locations (3)
- City of HopeDuarte, California
- UCLA / Jonsson Comprehensive Cancer CenterLos Angeles, California
- Stanford Cancer InstituteStanford, California