An Effective Drug Combination in pAML
Research type
Research Study
Full title
Determining an Effective Drug Combination in Paediatric AML
IRAS ID
325978
Contact name
Ken Mills
Contact email
Sponsor organisation
Queens University Belfast
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
0 years, 7 months, 24 days
Research summary
The survival rate for paediatric acute myeloid leukaemia (pAML) has improved vastly over this past few decades but has not yet exceeded ~70%. Furthermore, treatments are very toxic leading to long-term physical and developmental side-effects, which significantly affect the quality of life of pAML survivors. Therefore, there is an unmet need for effective, less toxic therapies for pAML.
To address this problem experimentally, we have applied a large drug screen, which involves the use of already FDA approved drugs in combination to identify an effective triple drug combination in pAML cell lines. As these drugs are already FDA approved, they have well reported toxicity profiles which are relatively better than current standard of care. Therefore, we are currently validating this drug combination in vitro (pAML cell lines grown in the lab). We have investigated the mechanism of cell death and concluded that it is a type of cell death called apoptosis. We have also investigated how sensitive a range of pAML cell lines are to the combination. There were a range of differing sensitivities, therefore we are currently investigating what underlying genetic mutations are inferring sensitivity or resistance to the combination as this will allow us to decipher targetable patient cohorts.
As our studies to date have been in vitro, our next steps will be to assess the combination in primary patient samples to further validate its efficacy in a model more representative of in vivo pAML.
REC name
West Midlands - Coventry & Warwickshire Research Ethics Committee
REC reference
23/WM/0068
Date of REC Opinion
3 Mar 2023
REC opinion
Favourable Opinion