Evaluation of CAR19 T-cells as an Optimal Bridge to Allogeneic Transplantation
Condition: Diffuse Large B-Cell Lymphoma
MeSH terms: Lymphoma, Large B-Cell, Diffuse
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to administer novel cluster of differentiation antigen 19 (CD19)
      specific Chimeric Antigen Receptor T-cells (CAR19 T-cells) to patients with relapsed or
      resistant Diffuse Large B Cell Lymphoma (DLBCL) to assess the safety and efficacy of this
      strategy as a bridge to allogeneic transplantation.
    

Detailed description: 
      Patients with Diffuse Large B Cell Lymphoma (DLBCL) resistant to or relapsing following
      rituximab-containing chemotherapy regimens have a poor prognosis. Patients may receive
      salvage chemotherapy and possibly an autologous stem cell transplant (auto-SCT). A proportion
      of these patients, however, will not respond to the chemotherapy or may relapse after the
      auto-SCT and therefore require novel treatment options. Such patients may benefit from an
      allogeneic stem cell transplantation (allo-STC).

      In this study the investigators aim to administer CAR19 T-cells to act as a bridge to the
      transplant strategy. Specifically, (1) the feasibility of generating CD19 specific Chimeric
      Antigen Receptor T-cells called CAR19 T-cells, (2) the safety of administering the CD19 CAR
      T-cells in this setting, (3) how well the CAR19 T-cells engraft and (4) to evaluate how
      effective these cells are as a bridge to allogeneic transplantation.

      Following informed consent and registration to the trial, patients will undergo an
      unstimulated leucapheresis for generation of the CAR19 T cells. Whilst the cells are being
      generated, patients will proceed with a further cycle of standard salvage (recommended
      ifosfamide, epirubicin and etoposide (i.e. the IVE regime), and should not receive rituximab.
      Patients will receive pre-conditioning with intravenous fludarabine and cyclophosphamide
      prior to infusion of a single dose of CAR-modified T-cells. An escalating dose protocol will
      be employed to identify a minimum effective dose of CAR19 T-cells.
    

Intervention name(s): Leukapheresis; Cyclophosphamide; Fludarabine; CAR19 T-Cells
Intervention type(s): Procedure; Drug; Drug; Biological
Intervention description(s): Patients will undergo leukapheresis prior to pre-conditioning chemotherapy to provide the immune cells required to produce the therapeutic product.; Patients will receive a standard pre-conditioning regime with cyclophosphamide 60mg/kg/day IV over 1 hour for 2 days (day-7 and day-6).; Fludarabine 25mg/m2/day IV over 15/30 minutes for 5 days (Day-5 to day-1).; The CAR19 T-cells are to be administered on day 0 at the dose specified by the Cancer Trials Centre (CTC) at the time of registration.
Three dose cohorts are planned:
Dose Level 1: 2x105 CAR19 T-cells/kg
Dose Level 2: 1x106 CAR19 T-cells/kg
Dose Level 3: 5x106 CAR19 T-cells/kg
Other intervention name(s): CD19 specific Chimeric Antigen Receptor T-cells
Intervention MeSH terms: Cyclophosphamide; Fludarabine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Relapsed; refractory; DLBCL