MOSAIC Trial
A multi-centre, double-blind, placebo-controlled randomised Phase II Trial to evaluate the effect of low dose decitabine and tetrahydrouridine in individuals with high-risk clonal haematopoiesis
NCT07435636
Project Status
Current
Indication
Clonal Cytopenia of Uncertain Significance (CCUS)
Clonal Haematopoiesis (CH)
Goal
Clonal haematopoiesis (CH) is characterised by the overproduction of blood cells derived from a single haematopoietic stem and progenitor cell (HSPC) harbouring certain somatic mutations. It is linked to serious outcomes, including cardiovascular disease, myeloid neoplasm (MN), and increased mortality. Cytopenia of Uncertain Significance (CCUS) is a CH subtype characterised by associated persistent cytopenia
CCUS is often asymptomatic. It affects approximately 10 % of people over 70 and is the most advanced precursor state with the highest risk of progressing to MN.
There is an unmet need to determine whether modifying CH can prevent adverse outcomes like MN. Current blood cancer therapies are too toxic for precursor conditions like CH. The MOSAIC trial will test a novel low-dose oral epigenetic therapy—decitabine with tetrahydrouridine (Dec+THU) in CCUS. In preclinical and early phase studies this combination has shown promise, with targeted, non-cytotoxic reversal of common CH mutations. The goal is to develop a safe and effective therapy in CCUS that restores normal blood cell production and prevents progression to MN.
Method
This randomised, placebo‑controlled, double‑blind trial will assess the novel intervention of decitabine combined with tetrahydrouridine in individuals with CCUS aged 60 to 85 years. The aim is to develop a safe and effective therapeutic approach that restores normal haematopoietic function and reduces the risk of progression to serious outcomes.
The trial plans to recruit 80 participants within the first 24 months, with approximately two years of follow‑up. Participants will attend monthly clinic visits for assessments and dispensing of either the study drug or placebo and will take the investigational product once weekly for 24 weeks before entering follow‑up.
CHOIR manages the clinical operations of the MOSAIC trial and is currently collaborating with other researchers from the Lowy Cancer Research Centre, University of New South Wales (UNSW) Sydney, Canberra Clinical Phenomics Service, Australian National University (ANU), the Leukaemia and Blood Cancer Research Unit, University of Auckland, and Treebough Therapies.
The study is funded by the Medical Research Future Fund (MRFF).
This trial is being conducted over 5 years in the NSW and the ACT.
Contact
Senior Trial Manager
Email: mosaic.jcsmr@anu.edu.au