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

University College London (UCL) logo

University College London (UCL)

Status and phase

Completed
Phase 1

Conditions

Diffuse Large B-Cell Lymphoma

Treatments

Procedure: Leukapheresis
Drug: Fludarabine
Biological: CAR19 T-Cells
Drug: Cyclophosphamide

Study type

Interventional

Funder types

Other

Identifiers

NCT02431988
UCL/14/0385
2015-000348-40 (EudraCT Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment

10 patients

Sex

All

Ages

16 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

  • Age 16-65 years
  • Confirmed diagnosis of CD19+ DLBCL
  • Primary resistant or relapsed disease failing to achieve metabolic Complete Response (CR) to 1st line salvage, or relapse post autograft failing to achieve metabolic CR following a single further cycle of salvage
  • Potential allogeneic transplant candidate
  • Agreement to have a pregnancy test, use adequate contraception for 12 months post-CAR19 T-cell infusion
  • Karnofsky performance status >60
  • Written informed consent

Exclusion criteria

  • Women who are pregnant or lactating
  • Prior allogeneic transplantation
  • Progressive disease following most recent salvage prior to planned leucapheresis (those with mixed response are eligible)
  • Prior history of ischaemic heart disease, dysrhythmias, abnormal electrocardiogram (ECG)(Left Bundle Branch Block (LBBB)), Multiple Gated Acquisition (MUGA) left ventricular ejection fraction (LVEF) <40%
  • Exclusions for proceeding to allogeneic transplantation (active hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV); liver function test (LFT) >3 x upper limit of normal (ULN); Creatinine Clearance (CrCl) <40 ml/min; or other comorbidity that precludes transplantation)
  • Known central nervous system (CNS) involvement or cerebral vascular accident (CVA) within prior 3 months
  • Patients receiving corticosteroids at a dose of > 10mg prednisolone per day (or equivalent)
  • Use of rituximab within the last 2 months prior to CAR19 T-cell infusion
  • Active autoimmune disease requiring immunosuppression
  • Life expectancy <3 months
  • Known allergy to albumin or dimethylsulfoxide (DMSO)
  • Any contraindication to the administration and use of ifosfamide, epirubicin, etoposide, fludarabine and cyclophosphamide.

Trial design

10 participants in 1 patient group

CAR19 T-cells
Experimental group
Description:
Patients will receive a single infusion of CAR19 T-cells following standard pre-conditioning with cyclophosphamide and fludarabine. The CAR19 T-cells are to be administered on day 0.
Treatment:
Drug: Cyclophosphamide
Biological: CAR19 T-Cells
Drug: Fludarabine
Procedure: Leukapheresis

Trial contacts and locations

0

Loading...

Data sourced from clinicaltrials.gov

Clinical trials

Find clinical trialsTrials by location

Resources

© Copyright 2024 Veeva Systems