Anti-CD19 Chimeric Antigen Receptor Modified T-cell (CAR-T) Therapy for Treatment of B-cell Hematological Malignancies

CAR-T therapy is now available as a commercial product for treatment of relapsed /refractory acute lymphoblastic leukaemia and B-lymphoma. There is limited access to this new treatment as the product is very expensive. It is imperative to develop cost effective, closed circuit manufacturing systems for CAR-T cells to make CAR-T cells a point-of care production option. Hong Kong Institute of Biotechnology has established a certified GMP facility and utilize the Prodigy system to manufacture CAR-T cells for clinical application. Prince of Wales Hospital and Hong Kong Children's Hospital will conduct the phase II clinical trial to confirm the efficacy and safety of local manufactured CAR-T cell product.

This is a pilot study of CD19 specific CAR-T cells produced by the CliniMACS prodigy system in treatment of paediatric and adult with relapsed or refractory Acute Lymphoblastic Leukemia (ALL) or B cell Non-Hodgkin Lymphoma (NHL). Our study aims to evaluate the safety and effectiveness of CD19 specific CAR-T cells produced by a closed circuit, point of care, manufacturing system to develop safe and effective CD19 specific CART cells for treatment of relapsed B cell NHL and relapsed refractory B cell ALL in children and adults. The CliniMACS plus system of Miltenyi Biotec is an automated cell separator with proven clinical efficacy. The CliniMACS prodigy system has been successfully used to generate a CD19 CAR T using lentiviral transduction with good efficiency of transduction and the activity of the CAR T cells. This pilot study using anti-CD19 CAR-T cells generated by the CliniMACS prodigy system will be undertaken in the Prince of Wales Hospital under the Department of Clinical Oncology, Department of Medicine, and the Department of Anatomical \& Cellular Pathology. Children will be managed at Hong Kong Children's Hospital. The subjects will comprise of paediatric and adult B cell ALL patients and cohort B of paediatric and adult B cell NHL patients. Eligible patients will go through Lymphapheresis procedures through central venous access. The cells will then be transferred to the CliniMACS prodigy system where they will be enriched and activated using the transAct CD3/CD28 Kit and transduced with a self-inactivating lentiviral vector encoding a CAR specific for CD19. The cells will be cultured, expanded and tested for efficiency of transduction, sterility and phenotype before preparation for patient use. The CAR-T cell treatment plan is consisted of a course of conditioning chemotherapy, followed by a single infusion of anti-CD19 CAR T cells after completion of conditioning / lymphodepletion chemotherapy. Patients will be observed as an inpatient for 7 days post treatment. Clinical status and progress of the patients, vital signs, blood counts, and blood chemistries will be monitored during and after CAR-T cell therapy. Occurrence of adverse events and serious adverse events will be recorded and managed with standard guidelines. Patients should be regularly followed up for at least two years after CAR T therapy. It is preferably to have long term follow-up of the patients beyond two years to look for any late complications