WT1 TCR Gene Therapy for Leukaemia: A Phase I/II Safety and Toxicity Study
WT1 TCR gene therapy is a new treatment for acute myeloid leukaemia and chronic myeloid leukaemia.
Patient's white blood cells (T cells) are modified to specifically fight the leukaemia cells by transferring a gene into the T cells, which allows them to recognize fragments of a protein called WT1. This protein is present on the surface of leukaemia cells at very high levels. The gene transferred to the T cells enables them to make a new T cell receptor (TCR), which will allow them to attack leukaemia cells with high levels of WT1 on their surface.
Using this form of gene therapy the investigators can convert some of the patient's immune system's own T cells into T cells that the investigators hope will be much more effective at recognizing and killing leukaemia cells.
|Acute Myeloid Leukaemia Chronic Myeloid Leukaemia||Genetic: WT1 TCR-transduced T cells||Phase 1 Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||WT1 TCR Gene Therapy for Leukaemia: A Phase I/II Safety and Toxicity Study|
- Identify organ toxicities and other side effects [ Time Frame: Up to 12 months per patient ]
- Transduction efficiency and TCR expression on TCR-transduced cells [ Time Frame: Up to 12 months per patient ]
- WT1-specific immune responses of TCR-transduced T cells [ Time Frame: Up to 12 months per patient ]
|Study Start Date:||April 2012|
|Estimated Study Completion Date:||October 2019|
|Estimated Primary Completion Date:||May 2019 (Final data collection date for primary outcome measure)|
Experimental: Single arm cohort study
WT1 TCR-transduced T cells
Genetic: WT1 TCR-transduced T cells
Two patient cohorts:
Cohort 1 (up to 6 patients) = ≤ 2 x 107/kg WT1 TCR-transduced T cells
Cohort 2 (12 patients)= ≤ 108/kg WT1 TCR-transduced T cells
This trial concerns a novel approach to generating leukaemia antigen-specific T cells for adoptive cellular therapy in HLA-A*0201 patients with acute myeloid leukaemia (AML) and chronic myeloid leukaemia (CML)
In this study, patient T cells will be gene-modified using a GMP grade retroviral vector containing the genes for a WT1-specific, HLA-A2-restricted T cell receptor. This ex vivo gene therapy will generate T cells expressing the WT1-specific TCR and thus able to recognise WT1-expressing target cells.
The autologous Cys1 WT1 TCR-transduced T cells will be re-infused back into adult leukaemia patients following lymphodepleting conditioning.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01621724
|Queen Elizabeth Hospital|
|Birmingham, United Kingdom, B15 2TH|
|University Hospitals Bristol NHS Foundation Trust|
|Bristol, United Kingdom, BS38 3AP|
|University College London Hospitals NHS Trust|
|London, United Kingdom, NW1 2PG|
|Royal Free Hospital NHS Trust|
|London, United Kingdom, NW3 2QG|
|Principal Investigator:||Emma Morris, Dr||University College, London|