Adult patients with r/r acute lymphoblastic leukemia (ALL) (stratum I), r/r Non-Hodgkin's lymphoma (NHL) including chronic lymphocytic leukaemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL) or mantle cell lymphoma (MCL) (stratum II) as well as paediatric patients with r/r ALL (stratum III) will be treated with autologous T-lymphocytes transduced by the third-generation RV-SFG.CD19.CD28.4-1BBzeta retroviral vector. The main purpose of this study is to evaluate safety and feasibility of escalating CD19.CAR T cell doses (0,1-20×20\^7 transduced cells/m\^2) after lymphodepletion with fludarabine and cyclophosphamide.
Confirmed CD19+ ALL, CLL, DLBCL, FL or MCL in patients ≥ 18 years
ALL (Ph+ and Ph-): Confirmed CD19+ ALL by cytology and flow cytometry (FACS) AND
Relapsed or refractory disease (including "molecular relapse" with minimal residual disease (MRD) levels > 10^-3 at two occasions > 2 weeks apart) with confirmed CD19 expression on malignant cells in relapse
Any relapse after allogeneic stem cell transplantation (alloSCT) (≥ 6 months from alloSCT at time of CAR T cell infusion) OR
Immunosuppressive medication with the exception of ≤ 30 mg prednisolone/d or equivalent at the time of CAR T cell transfusion
Bridging/maintenance therapy including chemo- and immunotherapy must be stopped ≥ 2 weeks prior to leukapheresis, but can be continued between leukapheresis and lymphodepletion
Intrathecal chemotherapy is possible at any time, but not during lymphodepletion until 14 days after CD19.CAR T cell transfusion
Any DLI must be completed > 6 weeks prior to CD19.CAR T cell infusion