NCT02431988

Evaluation of CAR19 T-cells as an Optimal Bridge to Allogeneic Transplantation

COBALT: Evaluation of CAR19 T-cells as an Optimal Bridge to Allogeneic Transplantation

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: University College, London · Academic / Other
• Sex: All
• Age: 16 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Conditions

• Diffuse Large B-Cell Lymphoma

Interventions

Type	Name	Description
PROCEDURE	Leukapheresis	Patients will undergo leukapheresis prior to pre-conditioning chemotherapy to provide the immune cells required to produce the therapeutic product.
DRUG	Cyclophosphamide	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).
DRUG	Fludarabine	Fludarabine 25mg/m2/day IV over 15/30 minutes for 5 days (Day-5 to day-1).
BIOLOGICAL	CAR19 T-Cells	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

Timeline

• Start date: 2016-06-01
• Primary completion: 2020-02-02
• Completion: 2022-03-21
• First posted: 2015-05-01
• Last updated: 2023-04-28

Locations

1 site across 1 country: United Kingdom