CD19-targeting, 3rd Generation CAR T Cells for Refractory B Cells Malignancy

Treatment of patients with B cell lymphoma or leukemia with two doses of CD19-targeting chimeric antigen receptor (CAR) T cells to evaluate for safety and efficacy. The CAR consists of a CD19 targeting antibody scFv with three intracellular signaling domains derived from CD3 zeta, CD28 and 4-1BB. Autologous T cells will be gene engineered with the CAR gene using a retrovirus vector. Prior to T cell infusion, the patients will be subjected to preconditioning treatment. After the second infusion patients will be subjected to immunomodulatory treatment. After T cell infusion, the patients will be evaluated for 24 months for adverse reactions, persistence of CAR T cells and efficacy. Primary outcome: \- Registration of the safety profile such as inflammation, fever, pain, changes in blood pressure, pulse and other adverse events. Weekly for the first 6 weeks, then at 3, 6, 9, 12, 15, 18, 21 and 24 months. Secondary outcome: Tumor response, CAR T cell persistence and immunological profile * Determination of tumor size and the tumor marker CD19. * Determination of the levels of circulating B cells. * Determination of the level of CAR T cells (mRNA and cells) in blood and biopsies. * Determination of activation markers on CAR T cells such as CD107a. * Determination of the presence of immunological markers in blood and biopsies. At 1 and 3 weeks then at 3, 6, 9, 12, 15, 18, 21 and 24 months.