Immunotherapy Using CAR T-cells to Target CD19 for Relapsed/Refractory CD19+ Primary CNS Lymphoma

The CAROUSEL Trial is a single-centre, non-randomised, open label Phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in adults (age ≥16) with relapsed/refractory Primary CNS Lymphoma. The study will evaluate the feasibility of generating the ATIMP, the safety of administering CD19CAR T-cell therapy and how effectively CD19CAR T-cells engraft, expand and persist following administration in patients with relapsed/refractory primary CNS lymphoma.

Inclusion Criteria: 1. Age ≥16 2. Patients with a histologically confirmed Diffuse Large B-Cell Lymphoma (DLBCL) confined to the CNS (Primary CNS Lymphoma (PCNSL)) 3. Relapsed\* or refractory CD19+ PCNSL, defined as disease progression following CR/CRu/PR, or failure to achieve PR, after one or more lines of a high-dose methotrexate-containing protocol \*Histological confirmation by re-biopsy at relapse is recommended if feasible. However, patients will be eligible without re-biopsy provided the initial diagnostic material is available and current MRI imaging features are consistent with PCNSL by neuroradiology review. 4. Measurable disease on contrast-enhanced MRI 5. Unsuitable for alternative salvage therapies as determined by their treating physician 6. Agreement to have a pregnancy test, use highly effective contraception (if applicable) 7. Written informed consent\*\* \*\* Some patients with PCNSL may be incapable of providing their own consent due to the neurological effects of their disease. In these cases a legal representative may be sought to provide consent'. Exclusion Criteria (Registration): 1. CD19 negative disease 2. Evidence of secondary CNS lymphoma 3. Prior allogeneic haematopoietic stem cell transplant 4. Active hepatitis B, C or HIV infection 5. Oxygen saturation ≤90% on air 6. Bilirubin \>2 x upper limit of normal 7. Glomerular Filtration Rate (GFR) \