TT52CAR19 / Great Ormond Street Hospital for Children - LARVOL DELTA

PBLTT52CAR19: TT52CAR19 Therapy for B-cell Acute Lymphoblastic Leukaemia (B-ALL) (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust | Active, not recruiting ➔ Completed

Trial completion • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

SINGLE CENTRE LONG-TERM OUTCOMES OF RELAPSED/REFRACTORY PAEDIATRIC B-ALL AFTER GENOME-EDITED ‘UNIVERSAL’ CAR19 T CELL THERAPY (EBMT 2024) - P1 | " Outcomes of paediatric patients (aged 0.8-16 years) treated at GOS between 2015 and 2022 with either UCART19 (1.1-4.6 x 106) or TT52CAR19 (0.8-2.0 x 106) CAR19 T cells/kg cells were surveyed...Our GOS augmented lymphodepletion (ALD) protocol comprising (total doses) fludarabine 150 mg/m2, cyclophosphamide 120 mg/kg, and alemtuzumab 1 mg/kg was used in 12/15 children... Longer term data for children treated at a single centre with genome-edited allogeneic CAR19 T cells indicate sustained remission in patients transplanted in molecular (PCR) MRD remission. Overall survival at our centre has been comparable to the wider autologous CAR19 setting, despite multiple lines of previous therapy, including CARs, Bi-specific T-cell engagers (BiTEs) and previous transplant. Notably, surviving subjects had all received augmented lymphodepletion ahead of CAR19 T cells, highlighting the importance of addressing host mediated barriers to mismatched cells for deep and rapid leukemic..."

Clinical • IO biomarker • Acute Lymphocytic Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Immunology • Pediatrics • Transplantation • CD4 • CD52

PBLTT52CAR19: TT52CAR19 Therapy for B-cell Acute Lymphoblastic Leukaemia (B-ALL) (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: 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

Enrollment closed • Trial completion date • Trial primary completion date • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Hematological Malignancies • Leukemia • Oncology

Phase 1 clinical trial of CRISPR-engineered CAR19 universal T cells for treatment of children with refractory B cell leukemia. (PubMed, Sci Transl Med) - P1 | "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."

Clinical • IO biomarker • Journal • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Graft versus Host Disease • Hematological Malignancies • Immunology • Inflammation • Leukemia • Oncology • Transplantation • CD19 • CD52

TT52CAR19: Phase 1 Trial of CRISPR/Cas9 Edited Allogeneic CAR19 T Cells for Paediatric Relapsed/Refractory B-ALL (ASH 2021) - "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."

IO biomarker • P1 data • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Bone Marrow Transplantation • Gene Therapies • Graft versus Host Disease • Hematological Malignancies • Immunology • Leukemia • Oncology • Pediatrics • Transplantation • CD19 • CD52