TT52CAR19

P1, N=9, Completed, Great Ormond Street Hospital for Children NHS Foundation Trust | Active, not recruiting --> Completed

P1, N=10, Active, not recruiting, Great Ormond Street Hospital for Children NHS Foundation Trust | Recruiting --> Active, not recruiting | Trial completion date: Jun 2022 --> Dec 2023 | Trial primary completion date: Jun 2022 --> Dec 2023

Three cell banks of TT52CAR19 T cells were generated and cryopreserved...Lymphodepletion included fludarabine, cyclophosphamide, and alemtuzumab and was followed by a single infusion of 0.8 × 10 to 2.0 × 10 CAR19 T cells per kilogram with no immediate toxicities...Other complications were within expectations, and primary safety objectives were met. This study provides a demonstration of the feasibility, safety, and therapeutic potential of CRISPR-engineered immunotherapy.

To date 2/4 children screened were found eligible and proceeded to lymphodepletion comprising Fludarabine, Cyclophosphamide and Alemtuzumab followed by a single infusion of 0.8-2.0x10 6 CAR19 T cells and a maximum of 5x10 4 /kg TCRαβ T cells. This child remains in remission >6 months later. Conclusions Feasibility of pre-manufacturing off-the-shelf CRISPR/Cas9 edited CAR19 T cells is demonstrated and the trial has provided first in human safety data and preliminary indications of potent anti-leukaemic activity in one of two subjects dosed.