ALLCAR19

• Research type

  Research Study

• Full title

  Immunotherapy for high risk/relapsed CD19+ Acute Lymphoblastic Leukaemia using CAR T-cells to target CD19

• IRAS ID

  217367

• Contact name

  Karl Peggs

• Contact email

  karl.peggs@ucl.ac.uk

• Sponsor organisation

  University College London

• Eudract number

  2016-004027-22

• Clinicaltrials.gov Identifier

  NCT02935257

• Duration of Study in the UK

  7 years, 8 months, 1 days

• Research summary

  Approximately 400 adults/year are diagnosed with Acute B-lymphoblastic leukaemia (B-ALL) and treated with chemotherapy. Many have good response, however 44% relapse. Allogeneic Haematopoietic Stem Cell Transplantation (allo-HSCT) represents the best chance for cure in these patients but it depends on donor availability, patient fitness and achievement of complete remission after ‘salvage’ chemotherapy. Even with allo-SCT, many patients relapse and survival is relatively poor (<40% of those undergoing the transplant). B-ALL relapse represents an area of great unmet clinical need.
  This study investigates whether patient’s immune cells (T-cells), that are genetically modified to recognise and target the leukaemia cells, can be safely used to treat relapsed B-ALL in adults. The modified cells are called CD19CAR T-cells. Early experience suggests that 70-90% of patients may respond to these cells, with 50% long term survival free from disease.
  We will take some of the patient’s white blood cells (which contain T-cells) and modify them in a laboratory with a virus that will make them express CD19 Chimeric Antigen Receptor (CD19CAR). This CD19CAR enables the T-cells to recognise CD19 protein (antigen) present on leukaemia cells (and normal B-cells). The modified T-cells will target the leukaemia cells once given back to the patient.
  Patients will first have chemotherapy with fludarabine and cyclophosphamide to help the CD19CAR T-cells grow once inside the patient. The CD19CAR T-cells will be administered as ‘split-dose’ (two intravenous infusions separated by 9 days) to reduce the risk developing severe toxicities associated with T cell activation. Patients will be closely monitored for side effects with regular tests/clinic visits.
  Common toxicity for CD19CAR T-cells is Cytokine Release Syndrome, which can be mild with ‘flu-like’ symptoms to severe (including fatal) with multi-organ failure, hypotension, respiratory compromise. It is reversible with good supportive care and Tocilizumab (antibody). Neurotoxicity of variable severity (aphasia, obtundation, delirium, seizures) has been reported and is usually transient (but fatalities have occurred). The CD19CAR T-cells may target the normal B cells (‘B-cell aplasia’) leading to increased risk of infection which is controlled with immunoglobulin replacement

• REC name

  London - West London & GTAC Research Ethics Committee

• REC reference

  17/LO/0117

• Date of REC Opinion

  6 Jun 2017

• REC opinion

  Further Information Favourable Opinion