Leukaemia is cancer of the white blood cells which are responsible for fighting infection. In leukaemia, the bone marrow produces abnormal levels of white blood cells. B-cell acute lymphoblastic leukaemia (B-ALL) is an aggressive (fast-growing) type of leukaemia in which too many B-cell lymphoblasts (immature white blood cells) are found in the bone marrow and blood. It is the most common type of ALL. Also called B-cell acute lymphocytic leukaemia and precursor B-lymphoblastic leukaemia.
Reuben Benjamin, MD, PhD King's College Hospital NHS Trust
ADIR, a Servier Group company
United States, Massachusetts
Massachusetts General Hospital, Boston, Massachusetts, United States, 02114
United States, Pennsylvania
Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, United States, 19104
United States, Texas
University of Texas MD Anderson Cancer Center, Houston, Texas, United States, 77030
France
Hôpital Saint-Antoine, PARIS Cedex 12, France, 75571
Hôpital Saint-Louis, Paris, France, 75010
Japan
Kyushyu University Hospital, Fukuoka, Japan, 812-8582
Hokkaido University Hospital, Sapporo, Japan, 060-8648
United Kingdom
King's College Hospital NHS Foundation Trust, London, United Kingdom, SE5 9RS
The Christie NHS Foundation Trust, Manchester, United Kingdom, M20 4BX
B-cell Acute Lymphoblastic Leukemia Disease InformationB-cell Acute Lymphoblastic Leukemia FrequencyThe PALL and CALM Trials: Phase 1 studies of UCART19 in Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) (Servier Sponsored)The Role of Gene Editing Within CAR T-Cell Therapy Development - Interview with Professor Waseem QasimLatest Gene Editing Clinical Trials for Cancer
Status: Completed
Description
The study is in two parts: a dose escalation then a safety dose expansion. The purpose of the dose escalation part is to evaluate the safety and tolerability of ascending doses of UCART19 (dose-escalation part) given as a single infusion in patients with relapsed / refractory (R/R) B-cell acute lymphoblastic leukaemia (B-ALL), to determine the maximum tolerated dose (MTD), the recommended dose and the lymphodepletion regimen. The purpose of the safety dose expansion is to assess the safety and tolerability of the RD for UCART19.
A preparation of allogeneic, frozen, ‘off-the-shelf’, universal transcription activator-like effector nuclease (TALEN)-engineered, gene-edited T lymphocytes expressing a chimeric antigen receptor (CAR) targeting the tumor-associated antigen (TAA) CD19, and containing a RQR8 transgene, with potential immunostimulating and antineoplastic activities. Using TALEN technology, the T-cell receptor (TCR) alpha chain and CD52 genes are deleted from the CAR19 T cells. Upon infusion, allogeneic universal CD19-specific CAR-modified T cells (UCART19) specifically target and bind to CD19-expressing tumor cells, thereby selectively lysing CD19-expressing tumor cells. CD19 antigen is a B-cell specific cell surface antigen expressed in all B-cell lineage malignancies. Deletion of the CD52 gene makes the modified donor T cells resistant to the anti-CD52 monoclonal antibody alemtuzumab, which is used during lymphodepletion. The knockout of the TCR alpha gene eliminates TCR expression and is intended to abrogate the potential induction of graft-versus-host disease (GvHD) by the donor T cells. The gene-edited allogeneic, frozen UCART19 have reduced production times and provide off-the-shelf CAR-T cells when compared to autologous CAR-T cells, which use the patient's own cells and are produced on an individual basis. The protein expressed by the RQR8 transgene contains epitopes from CD34 and CD20, which allows tracking of the UCART19 cells with a clinically-approved anti-CD34 antibody. Additionally if the UCART19 cells cause unacceptable side effects, the CD20 portion of the protein permits selective depletion of the UCART19 cells when the anti-CD20 monoclonal antibody rituximab is administered.
Last updated: Apr. 20, 2024