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.
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
Presence of supplemental oxygen, cardiac pacemaker
Known allergic reactions to components of the anti-CD19 CAR T cell product as evidenced by prior documented anaphylactic reaction or other clinical signs and/or symptoms of an allergic reaction as determined by the PI
Febrile illness within 3 days of admission for lymphodepleting conditioning therapy
Treatment with another investigational drug or other investigational intervention within 2 weeks of apheresis
Parallel
Chimeric Antigen Receptor T-Cell Therapy
Biological/VaccineGiven CD19 CAR T cells IV
Cyclophosphamide
DrugGiven IV
Fludarabine Phosphate
DrugGiven IV
Rituximab
Biological/VaccineGiven IV
6
Treatment groupsSee each treatment group below.
Proportion of products successfully manufactured meeting the established release criteria with a goal of at least 1.0 x 10^6 cells/kilogram
Incidence and severity of adverse events related to lymphodepleting chemotherapy and or CD19 chimeric antigen receptor (CAR) T cells
Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate. Toxicity data by type and severity will be summarized by frequency tables.
Dose limiting toxicities (DLTs) related to lymphodepleting chemotherapy and or CD19 CAR T cells
Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate. Toxicity data by type and severity will be summarized by frequency tables.
Maximum tolerated dose
Incidence of toxicities related to CD19 CAR T cells
Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate. Toxicity data by type and severity will be summarized by frequency tables.
Overall response rate
Defined as the percentage of patients that achieve partial response or complete response. Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate.
Complete response rate
Logistic regression will be utilized to assess the effect of patient prognostic factors on the response rate and the toxicity rate.
Overall survival
Will be estimated using Kaplan and Meier methods. Comparison of time-to-event endpoints by important subgroups will be made using the log-rank test.
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University of California, Davis
Lead sponsor
National Cancer Institute (NCI)
Collaborator
