Immune mechanisms in patients with Chronic Myeloid Leukaemia
Research type
Research Study
Full title
Immune mechanisms in patients with chronic myeloid leukaemia (CML)
IRAS ID
242942
Contact name
Hugues de Lavallade
Contact email
Sponsor organisation
Guy's & St Thomas' Foundation NHS Trust R&D Department
Clinicaltrials.gov Identifier
NA, NA
Duration of Study in the UK
5 years, 2 months, 1 days
Research summary
Chronic Myeloid Leukaemia (CML) is a clonal disorder in which the prognosis has been dramatically improved by the use of targeted therapy, namely tyrosine kinase inhibitors (TKIs).
Some patients can stop their treatment with TKIs after taking these for a number of years, but the majority of patients have persisting disease detected using molecular techniques and approximately 60% of them will experience a molecular relapse. The underlying mechanism for this relapse is unknown and there have been a number of hypotheses to understand why some patients who stop TKIs do not experience molecular relapse.
It is possible that the patient’s immune system may be able to control the disease after stopping treatment as suggested by the fluctuation of low residual disease by molecular techniques.We plan to analyse different components of the immune system functionally and quantitatively to have a better understanding of this. Since we have previously shown a potent effect of TKIs on some subsets of the immune system we will also study whether this effect is reversible. This will form the rationale for the use of new medications that stimulate the immune system – known as immune-modulatory drugs, such as immune checkpoint inhibitors – in these patients which we also plan to investigate further.
The other hypothesis to explain why some patients do not experience relapse after stopping treatment is the possibility of a complete eradication or exhaustion of leukaemic stem cells (LSC) - the cells that give rise to the leukaemia, and we plan to also investigate this further. This project may help in identifying biomarkers to predict disease relapse as well as bring insight to choose additional therapies to increase disease control in patients with CML.
REC name
West of Scotland REC 3
REC reference
18/WS/0146
Date of REC Opinion
30 Aug 2018
REC opinion
Further Information Favourable Opinion