CAROUSEL
Research type
Research Study
Full title
Immunotherapy using CAR T-cells to target CD19 for relapsed/refractory CD19+ Primary CNS Lymphoma
IRAS ID
283938
Contact name
Claire Roddie
Contact email
Sponsor organisation
University College London
Eudract number
2020-001698-63
Clinicaltrials.gov Identifier
Duration of Study in the UK
12 years, 3 months, 0 days
Research summary
Primary CNS lymphoma (PCNSL) accounts for 2.4-3% of brain tumours in the UK. Significant progress has been made in managing newly diagnosed patients. Relapsed/refractory(r/r) PCNSL remains a major unmet need, with patients having a median overall survival of 3.5 months. Autologous stem cell transplant or whole brain radiotherapy is recommended for patients who achieve second remission, however the majority of patients do not. With the added challenge of crossing the blood-brain barrier (BBB), novel therapeutic options are required.
CAROUSEL investigates whether a patient’s immune cells (T-cells), that are genetically modified to target lymphoma cells, can be safely used to treat r/r PCNSL. The modified cells are called CD19CAR T-cells.
We will take some of the patient’s T-cells and modify them with a virus to make them express CD19 Chimeric Antigen Receptor (CD19CAR). This CD19CAR enables the T-cells to recognise CD19 protein present on lymphoma cells and attack them once given back to the patient.
Patients will have pre-conditioning therapy to help the CD19CAR T-cells grow once inside the patient. The CD19CAR T-cells will then be given as intravenous infusion. Patient’s disease will be assessed 1 month after CD19CAR T infusion. If their lymphoma has decreased, they will be regularly seen for 2 years but no further treatment will be given.
The BBB may limit the number of CD19CAR T-cells that reach the brain when they are given intravenously. To increase the chance of CD19CAR T-cells targeting the lymphoma cells, patients whose disease has not responded to the intravenous infusion (and in the absence of significant toxicity), may have a 2nd CD19CAR T dose into the brain, via an Ommaya reservoir (intraventricular infusion).
Common toxicity for CD19CAR T-cells is Cytokine Release Syndrome, which can range from mild ‘flu-like’ symptoms to severe (including fatal) multi-organ failure. It is reversible with supportive care and Tocilizumab. Neurotoxicity of variable severity is a known side-effect and is usually transient (but fatalities have occurred). CD19CAR T-cells also target normal B cells, leading to increased infection risk which is controlled with immunoglobulin replacement.REC name
London - West London & GTAC Research Ethics Committee
REC reference
20/LO/1053
Date of REC Opinion
29 Sep 2020
REC opinion
Favourable Opinion