Immunotherapy using CAR T-cells to target CD19 for relapsed/refractory CD19+ Primary CNS Lymphoma
Description
Design:
A single centre, non-randomised, open label phase I clinical trial of an Advanced Therapy Investigational Medicinal Product (ATIMP) in patients 16 years and above with relapsed/refractory CD19+ Primary CNS Lymphoma. The ATIMP tested in this study is CD19CAT-41BBζ CAR T-cells (referred to as CD19CAR T-cells). These are Chimeric Antigen Receptor (CAR) T-cells genetically modified to recognise the CD19 protein present on the malignant cells and attack them.
A total of 12 patients will be treated at 1 participating site.
Treatment:
Patients will undergo an unstimulated leucapheresis which will be sent to CCGTT-RFH for manufacture of CD19CAR T-cells. ATIMP manufacture takes about 15 days. During this period, patients may receive “holding” chemotherapy to maintain disease control. Prior to CD19CAR T-cell infusion patients will receive iv cyclophosphamide 60mg/kg on Day-6 and iv fludarabine 30 mg/m2 on Days -5 to -3, followed by conditioning with i.v. pembrolizumab 200mg on Day-1.The CD19CAR T-cells will be given in two themes. All patients will receive a single dose of 250 x 10^6 CD19CAR T-cells in theme 1 (intravenous infusion).
Patients whose disease does not respond to this intravenous infusion (or comes back (relapses) later) and in the absence of toxicity, may receive a second dose of 25 x 10^6 CD19CAR T-cells infusion in theme 2 (intraventricular infusion delivered into the brain using Ommaya reservoir).
Patients will be followed up regularly (with daily, weekly and monthly visits) until 2 years post-CD19CAR T-cell infusion. After 2 years patients will continue to be followed up annually until 10 years post ATIMP infusion.
Key inclusion/exclusion criteria:
Age 16 or over; diagnosis of Relapsed or refractory CD19+ PCNSL.Patients with active HepB, HepC or HIV infection; with evidence of secondary CNS lymphoma are excluded from the study. Bilirubin needs to be no more than 2xULN, ECOG must not be 3-4 and GFR must be
Duration of recruitment:
Anticipated recruitment for the feasibility will be over 2 years.
Aim
The aim of the study is to evaluate the safety, efficacy and duration of response of the CAR T-cells in resistant or relapsed PCNSL.