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
| Registry | NCT07435636, acronym MOSAIC |
|---|---|
| Status | Not yet recruiting |
| Phase | Phase 2 |
| Study type | Interventional; randomized, parallel, masking: quadruple, treatment |
| Enrollment | 80 (Estimated) |
| Sponsor | Clinical Hub for Interventional Research (CHOIR) (Other gov); collaborators: Medical Research Future Fund, Australian National University, University of Auckland, New Zealand, Treebough Therapies, The University of New South Wales |
| Conditions | Clonal Cytopenia of Uncertain Significance, CCUS Clonal Cytopenia of Undetermined Significance, Clonal Hematopoiesis |
| Interventions | Oral Decitabine and Tetrahydrouridine, Matched Placebo (Capsules) (Drug) |
| Dates | start 2026-04-13 (estimated), primary completion 2030-04-14 (estimated), completion 2030-10-01 (estimated), first posted 2026-02-27, last updated 2026-02-27 |
| Locations | 3 sites in Australia |
Related Papers Related Patents Related Grants Related Experts
All trials for Clonal Cytopenia of Uncertain Significance All trials for CCUS Clonal Cytopenia of Undetermined Significance All trials of Oral Decitabine and Tetrahydrouridine All trials of Matched Placebo (Capsules)
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.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| active drug | Experimental | Drug: Oral Decitabine and Tetrahydrouridine | Oral combination capsules containing both decitabine and tetrahydrouridine (Dec+THU) |
| matched placebo | Placebo comparator | Drug: Matched Placebo (Capsules) |
Sex: All, ages: 60 Years to 85 Years
Inclusion Criteria: 1. Age ≥ 60 and ≤ 85 years old 2. Clonal Cytopenia of Uncertain Significance (CCUS), defined by all of the following: a. Persistent cytopenia, present on at least two occasions, at least four months apart, with no other cause identified: i. Hemoglobin (Hb) < 120 g/L in people born female, and < 130 g/L in people born male ii. Platelet count < 150 x 109/L iii. Absolute Neutrophil Count (ANC) < 1.8 x109/L b. Clonal hematopoiesis (CH) driver mutation confirmed by custom gene panel mutation analysis c. absence of features diagnostic for defined myeloid neoplasm (MN) on bone marrow examination 3. CH driver mutation variant allele fraction (VAF) of ≥ 10% 4. For participants living with HIV: 1. Receiving and adherent to suppressive antiretroviral therapy for at least 12 months 2. CD4+T cell count ≥ 0.35 x 109/L 3. HIV viral load < 50 copies/mL 6\. Performance status by Eastern Cooperative Oncology Group (ECOG) Criteria of 0 or 1 7. For participants who are of childbearing potential, or whose partners are of childbearing potential: 1. Agreement to use at least two highly effective (per Clinical Trial Facilitation Group) contraceptive methods throughout the course of the trial, and for 6 months following the last dose of trial drug 2. Refrain from donating eggs or sperm during the same period 3. Confirmation of a negative serum pregnancy test at screening and at the beginning of each treatment cycle visit (for female participants of childbearing potential) 8. Provision of signed written informed consent document prior to any trial-related assessments or procedures being carried out Exclusion Criteria: 1. ANC < 0.5 x109/L 2. Serum AST (Aspartate transaminase) or ALT (Alanine aminotransaminase) > 3 times of upper limit of normal 3. Calculated or measured creatinine clearance ≤ 50 mL/min 4. Significant active cardiac disease within the previous 6 months, including: 1. New York Heart Association (NYHA) class III or IV congestive heart failure 2. Unstable angina or angina requiring surgical or medical intervention 3. Myocardial infarction 4. New or unstable cardiac arrhythmia. Stable or controlled arrhythmias are permitted 5. Active systemic infections: 1. Infection with ongoing signs/symptoms related to the infection without improvement despite appropriate anti-infectives 2. Active Hepatitis B infection (HBV) (defined as HBsAg positive, or HBcAb positive and measurable HBV DNA; participants who are HBcAb positive must have HBV DNA assayed during screening) 3. Active Hepatitis C Virus (HCV) will be ineligible if there is clinical hepatic dysfunction or other systemic manifestations of HCV disease, or if the hepatic eligibility parameters above are not met. Consideration should be given to curative HCV therapy prior to enrolment in consultation with HCV clinician 6. Any history of hematological or solid malignancy in previous the 5 years unless the participant has been free of disease for ≥ 36 months. However, participants with the following history/concurrent conditions are not excluded: 1. Basal or squamous cell carcinoma of the skin 2. Carcinoma in situ of the cervix 3. Carcinoma in situ of the breast 4. Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis \[TNM\] clinical staging system) 7. Known hypersensitivity to trial drugs or their constituents 8. Currently enrolled in the treatment phase of an interventional investigational trial. 9. Pregnant or breast-feeding individuals 10. Any condition not already outlined above which, in the opinion of the Principal Investigator, would place the participant at risk if they participated or would jeopardize adherence, follow up, or confound the ability to interpret trial data
| Facility | City | Country | Status |
|---|---|---|---|
| Canberra Health Services | Canberra, Australian Capital Territory | Australia | |
| Prince of Wales Hospital | Randwick, New South Wales | Australia | |
| Westmead Hospital | Westmead, New South Wales | Australia |