A Phase 1 Study to Evaluate Intracerebroventricular (ICV) Administration of CD19-Targeting Chimeric Antigen Receptor (CAR) T Cells in Patients With CNS Lymphoma
City of Hope Medical Center
Summary
This phase I trial tests the safety, side effects, and best dose of intracerebroventricularly (ICV) administered CD19-chimeric antigen receptor (CAR) T cells in treating patients with central nervous system (CNS) lymphoma. 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 cancer cells. T cells are taken from a patient's blood. Then the gene for a special receptor that binds to a certain protein, CD19, on the patient's cancer cells is added to the T cells in the laboratory. The special receptor is called a chimeric antigen receptor (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. ICV is an injection technique that delivers the CD19-CAR T cells directly into the cerebrospinal fluid (which flows in and around the hollow spaces of the brain and spinal cord, and the thin layers of tissue that cover and protect the brain and spinal cord) in the brain, through a surgically placed catheter. Giving CD19-CAR T cells ICV may be more effective at treating patients with CNS lymphoma than giving them via other methods.
Description
PRIMARY OBJECTIVES: I. Examine and describe the safety and feasibility of ICV delivery of CD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem T-lymphocytes (CD19-CAR T cells) and determine the recommended phase 2 dose (RP2D) in participants with primary CNS lymphoma, or secondary lymphoma with CNS only relapse. II. Determine the activity of ICV-delivered CD19-CAR T cells based on disease response at the maximum tolerated dose (MTD). SECONDAY OBJECTIVES: I. Describe persistence, expansion and phenotype of endogenous and CD19-CAR T cells in peripheral blood (PB), and cerebral spinal fluid (CSF), wh…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Participant must have the ability to understand and the willingness to sign a written informed consent * Note: For research participants who do not speak English, a short form consent may be used with a City of Hope (COH) certified interpreter/translator to proceed with screening and leukapheresis, while the request for a translated full consent is processed. However, the research participant can proceed with lymphodepletion (if applicable) and CAR T cell infusion only after the translated full consent form is signed * Agreement to allow the use of archival tissue fro…
Interventions
- ProcedureAspiration
Undergo CSF aspiration
- ProcedureBiospecimen Collection
Undergo blood sample collection
- ProcedureCatheterization
Undergo catheterization
- BiologicalCD19CAR-CD28-CD3zeta-EGFRt-expressing Tn/mem T-lymphocytes
Given ICV
- ProcedureComputed Tomography
Undergo CT
- DrugCyclophosphamide
Given IV
- DrugFludarabine
Location
- City of Hope Medical CenterDuarte, California