Clonal hematopoiesis (CH) is characterized by the overproduction of blood cells derived from a single hematopoietic stem and progenitor cell (HSPC) harboring certain somatic mutations. It is linked to serious outcomes, including cardiovascular disease, myeloid neoplasm (MN), and increased mortality.
Clonal Cytopenia of Uncertain Significance (CCUS) is a CH subtype characterized by associated persistent cytopenia. 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. Current blood cancer therapies are too toxic for precursor conditions like CH.
MOSAIC is a randomized double-blind placebo-controlled trial that will test a novel low-dose oral epigenetic therapy-decitabine with tetrahydrouridine (Dec+THU) in CCUS. It has shown targeted, non-cytotoxic reversal of common CH mutations in preclinical and early-phase studies.
The goal is to develop a safe and effective therapy in CCUS that restores normal blood cell production and prevents progression.
Age ≥ 60 and ≤ 85 years old
CH driver mutation variant allele fraction (VAF) of ≥ 10%
Receiving and adherent to suppressive antiretroviral therapy for at least 12 months
CD4+T cell count ≥ 0.35 x 109/L
ANC < 0.5 x109/L
Serum AST (Aspartate transaminase) or ALT (Alanine aminotransaminase) > 3 times of upper limit of normal
Calculated or measured creatinine clearance ≤ 50 mL/min
New York Heart Association (NYHA) class III or IV congestive heart failure
Clinical Hub for Interventional Research (CHOIR)
Lead sponsor
Medical Research Future Fund
Collaborator
Australian National University
Collaborator
University of Auckland, New Zealand
Collaborator
Treebough Therapies
Collaborator
The University of New South Wales
Collaborator