A Phase I Study to Evaluate the Safety of Escalating Doses of Lymphodepleting Conditioning Chemotherapy Prior to CD19 Chimeric Antigen Receptor T Cells in Subjects With Relapsed/Refractory Diffuse Large B-cell Lymphoma
Mehrdad Abedi, MD
Summary
This phase I trial evaluates the best dose, possible benefits and/or side effects of fludarabine and cyclophosphamide with or without rituximab before CD19 chimeric antigen receptor T cells in treating patients with diffuse large B-cell lymphoma that has come back (relapsed) or has not responded to previous treatment (refractory). T-cells are a normal part of the immune system. To make the T-cell medication, T-cells are taken from the blood and altered in a laboratory. They are then returned to the body. The altered T-cells will latch on to a specific part of the cancer cells and hopefully kill them. Once the T-cells have been altered in the laboratory, they are called "CAR T-cells." CAR is short for "chimeric antigen receptors." These are structures on the surface of cells that allow the altered T-Cells to find and destroy the cancer cells. Another part of the T-Cell medication is called "CD19." This part is called a "biomarker." Biomarkers help doctors determine whether a cancer is getting worse and whether medications are working to stop it. The chemotherapy drugs that are given before the T-Cell therapy are cyclophosphamide, fludarabine and rituximab. Rituximab is an immunotherapy drug. These chemotherapy drugs will reduce the number of normal (unaltered) T-Cells in the body to make room for the altered T-cells to kill the cancer cells. Giving fludarabine and cyclophosphamide with or without rituximab before CD19 CAR T cell therapy may help improve response to CD19 CAR T cell therapy in patients with diffuse large B-cell lymphoma.
Description
PRIMARY OBJECTIVES:I. To examine the feasibility to manufacture autologous CD19 CAR T cells at a minimum target dose of 1.0 x 10\^6 cells/kilogram using the CliniMACS automated system.II. To determine the safety of administering high-dose conditioning chemotherapy with cyclophosphamide and fludarabine with rituximab prior to CD19 CAR-T cell therapy in patients with relapsed (R)/refractory (R) diffuse large B cell lymphoma (DLBCL) and to find the recommended regimen after phase II dose for this therapy.III. To determine the safety of infusion of chimeric antigen receptor T cells targeting CD19…
Eligibility
- Age range
- 18+ years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study * Commercial CD19 CAR T cell product not available for the patient * Male or female, aged \>= 18 * In good general health as evidenced by medical history or as determined by the principal investigator (PI) * Ability to swallow oral medication and willingness to adhere to the study intervention and any required medications * For females of reproductive potential: use of highly effective contraception (oral contraceptiv…
Interventions
- BiologicalChimeric Antigen Receptor T-Cell Therapy
Given CD19 CAR T cells IV
- DrugCyclophosphamide
Given IV
- DrugFludarabine Phosphate
Given IV
- BiologicalRituximab
Given IV
Location
- University of California Davis Comprehensive Cancer CenterSacramento, California