Clonal Cytopenia of Uncertain SignificancePhase 2MOSAICNCT07435636
Modulation of Stem Cell Differentiation in Individuals With High Risk Clonal Haematopoiesis
A Phase 2 study testing Oral Decitabine and Tetrahydrouridine in people with Clonal Cytopenia of Uncertain Significance and CCUS Clonal Cytopenia of Undetermined Significance, run by Clinical Hub for Interventional Research (CHOIR) at 3 sites in Australia.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 60 to 85 years
- Conditions the study is for
- Clonal Cytopenia of Uncertain Significance, CCUS Clonal Cytopenia of Undetermined Significance, Clonal Hematopoiesis
- What is being tested?
- Oral Decitabine and Tetrahydrouridine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 3 sitesAustralia
- Study dates
- 1 Dec 2026to Dec 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 60 and ≤ 85 years old
- Clonal Cytopenia of Uncertain Significance (CCUS), defined by all of the following:
- 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
- CH driver mutation variant allele fraction (VAF) of ≥ 10%
- For participants living with HIV:
- Receiving and adherent to suppressive antiretroviral therapy for at least 12 months
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- CD4+T cell count ≥ 0.35 x 109/L
- 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:
- 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
- Refrain from donating eggs or sperm during the same period
- 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
Who cannot join
- 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
- Significant active cardiac disease within the previous 6 months, including:
- New York Heart Association (NYHA) class III or IV congestive heart failure
- Unstable angina or angina requiring surgical or medical intervention
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- Myocardial infarction
- New or unstable cardiac arrhythmia. Stable or controlled arrhythmias are permitted
- Active systemic infections:
- Infection with ongoing signs/symptoms related to the infection without improvement despite appropriate anti-infectives
- 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)
- 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
- 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:
- Basal or squamous cell carcinoma of the skin
- Carcinoma in situ of the cervix
- Carcinoma in situ of the breast
- Incidental histologic finding of prostate cancer (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system)
- Known hypersensitivity to trial drugs or their constituents
- Currently enrolled in the treatment phase of an interventional investigational trial.
- Pregnant or breast-feeding individuals
- 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
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Australia3 sites
Canberra Health Services
Canberra, Australian Capital Territory, 2605
Professor Mark Polizzotto, +61000000000, mosaic.jcsmr@anu.edu.au
Prince of Wales Hospital
Randwick, New South Wales, 2031
Dr Annmarie Bosco, +61000000000
Westmead Hospital
Westmead, New South Wales, 2145
Dr Lachlin Vaughan, +61000000000
About this study
Official title: 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
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.
Read more
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.
- Conditions
- Clonal Cytopenia of Uncertain Significance, CCUS Clonal Cytopenia of Undetermined Significance, Clonal Hematopoiesis
- Being tested
- Oral Decitabine and Tetrahydrouridine, Matched Placebo (Capsules)
- Keywords
- MOSAIC, CH, Modulation of stem cell differentiation, CCUS, persistent cytopenia, clonal hematopoiesis, clonal haematopoiesis, Clonal Cytopenia of Uncertain Significance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oral Decitabine and TetrahydrouridineDrug
After randomization, participants will receive oral combination capsules containing decitabine (Dec) (2.5 mg) and tetrahydrouridine (THU) (125 mg) minitablets, or matched placebo. Trial medication will be dispensed on Day 1 of each cycle and taken once weekly (Days 1, 8, 15, 22) for 24 weeks. Dosing of Dec+THU will follow weight-based dosing at 0.2mg/kg and 10mg/kg respectively. This is a phase II, multicenter, double-blind, placebo-controlled randomized trial
Matched Placebo (Capsules)Drug
Placebo capsules will be administered on the same schedule and dosing frequency to the active drug
| Study group | Role | What they receive |
|---|---|---|
| active drug | Experimental | Oral combination capsules containing both decitabine and tetrahydrouridine (Dec+THU) Receives: Drug: Oral Decitabine and Tetrahydrouridine |
| matched placebo | Placebo comparator | Not described Receives: Drug: Matched Placebo (Capsules) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in variant allele fraction (VAF) in peripheral blood mononuclear cells (PBMC) at the completion of 24 weeks of treatment.
Change in variant allele fraction (VAF) in peripheral blood mononuclear cells (PBMC), at the completion of 24 weeks of treatment, will be used to compare the evolution of clonal cytopenia of undetermined significance (CCUS) in individuals with CCUS and associated clinically significant cytopenia receiving Dec+THU compared with those receiving placebo, by intention-to-treat analysis.
VAF will be assessed by capture sequencing using the Auckland Myeloid Gene Panel V4 (AMGPV4)
Measured: End of Treatment (Week 24)
Secondary outcomes (8)
Number and proportion of participants: a) experiencing Grade 3, 4 and 5 adverse events (AE) b) discontinuing treatment due to AEs or Serious Adverse Events (SAEs) c) living with HIV maintaining HIV Viral Load (VL) suppression
The safety profile of Dec+THU treatment will be evaluated at the end of 24 weeks of treatment. Each cycle is 28 days.
Measured: End of Treatment (Week 24)
Number and proportion of participants completing planned 24 weeks of treatment.
The feasibility of Dec+THU treatment will be evaluated by number and proportion of participants completing planned 24 weeks of treatment
Measured: End of Treatment (Week 24)
Number and proportion of participants with cytopenia response
Participant cytopenia response will be assessed and measured according to the 2018 International Working Group (IWG) criteria with comparison between the Dec+THU treatment group and the placebo group
Measured: End of Treatment (Week 24) and Follow Up 1 (Week 48)
Duration of cytopenia response
Duration of cytopenia response will be assessed and measured according to the 2018 International Working Group (IWG) criteria with comparison between the Dec+THU treatment group and the placebo group
Measured: End of Treatment (Week 24) and Follow Up Visit 1 (Week 48)
Changes in VAF in subgroups defined by cytopenias and baseline mutations
VAF will be measured to compare changes in VAF in subgroups defined by baseline cytopenias and baseline mutations.
DNA extracted from the peripheral blood will be sequenced after NGS library preparation and target-enrichment with a custom capture panel (Agilent Sure Select). Next Generation Sequencing (NGS) will be performed and the number of variant reads at a given position will be used to calculate the VAF. VAF will be a direct measure of the fraction of cells carrying the variant in the sample used for DNA extraction.
Measured: Baseline (Week 0), at the start of Cycle 4 Day 1 (Week 12) (each cycle is 28 days), End of Treatment (Week 24), Follow Up Visit 1 (Week 48) and Follow Up Visit 2 (Week 96)
Changes in peripheral blood VAF
Peripheral blood VAF will be measured at timepoints to compare changes in VAF between the Dec+THU treatment group and placebo group
DNA extracted from the peripheral blood will be sequenced after NGS library preparation and target-enrichment with a custom capture panel (Agilent Sure Select). Next Generation Sequencing (NGS) will be performed and the number of variant reads at a given position will be used to calculate the VAF. VAF will be a direct measure of the fraction of cells carrying the variant in the sample used for DNA extraction.
Measured: Baseline (Week 0), at the start of Cycle 4 Day 1 (Week 12) (each cycle is 28 days), End of Treatment (Week 24), Follow Up Visit 1 (Week 48), Follow Up Visit 2 (Week 96)
Changes in the levels of inflammatory cytokines between treatment groups in peripheral blood and bone marrow.
Inflammatory cytokine profile changes will be compared between the Dec+THU treatment group and placebo group in peripheral blood and bone marrow.
Serum and plasma will be extracted from participant bone marrow and peripheral blood samples for quantifying inflammatory cytokines levels to compare inflammatory cytokines profile changes between the treatment groups.
Measured: Baseline (Week 0), at the start of Cycle 4 Day 1 (Week 12) (each cycle is 24 weeks), End of Treatment (Week 24), Follow Up Visit 1 (Week 48), Follow Up Visit 2 (Week 96)
Changes in bone marrow (BM) VAF
This comparison will be made by measuring bone marrow VAF to determine if there are any changes between treatments groups at screening and end of treatment.
DNA extracted from the bone marrow will be sequenced after NGS library preparation and target-enrichment with a custom capture panel (Agilent Sure Select). Next Generation Sequencing (NGS) will be performed and the number of variant reads at a given position will be used to calculate the VAF. VAF will be a direct measure of the fraction of cells carrying the variant in the sample used for DNA extraction.
Measured: Screening, End of Treatment (Week 24)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2026
- Study start1 Dec 2026 (estimated)
- Primary completion1 Dec 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clonal Cytopenia of Uncertain SignificanceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Clinical Hub for Interventional Research (CHOIR)
- Sponsor type
- Other government
- Collaborators
- Medical Research Future Fund, Australian National University, University of Auckland, New Zealand, Treebough Therapies, The University of New South Wales
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07435636
- Sponsor's protocol ID
- 24-CH-002
- Acronym
- MOSAIC
- Status last verified
- Nov 2026
- First submitted
- 17 Feb 2026
- Last updated
- 4 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07435636
- Acronym / sponsor ID
- MOSAIC / 24-CH-002
- Conditions
- Clonal Cytopenia of Uncertain Significance, CCUS Clonal Cytopenia of Undetermined Significance, Clonal Hematopoiesis
- Keywords
- MOSAIC, CH, Modulation of stem cell differentiation, CCUS, persistent cytopenia, clonal hematopoiesis, clonal haematopoiesis, Clonal Cytopenia of Uncertain Significance
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Clinical Hub for Interventional Research (CHOIR)Other government
- Collaborators
- Medical Research Future Fund, Australian National University, University of Auckland, New Zealand, Treebough Therapies, The University of New South Wales
- Study start
- 1 Dec 2026 (estimated)
- Primary completion
- 1 Dec 2030 (estimated)
- Study completion
- Dec 2030 (estimated)
- First posted
- 27 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| active drug | Experimental | Drug: Oral Decitabine and TetrahydrouridineOral combination capsules containing both decitabine and tetrahydrouridine (Dec+THU) |
| matched placebo | Placebo comparator | Drug: Matched Placebo (Capsules) |
Who may qualify
- Ages
- 60 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Age ≥ 60 and ≤ 85 years old
- Clonal Cytopenia of Uncertain Significance (CCUS), defined by all of the following:
- CH driver mutation variant allele fraction (VAF) of ≥ 10%
- For participants living with HIV:
- 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:
Key exclusion criteria (21 listed)
- 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
- Significant active cardiac disease within the previous 6 months, including:
- Active systemic infections:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oral Decitabine and TetrahydrouridineAfter randomization, participants will receive oral combination capsules containing decitabine (Dec) (2.5 mg) and tetrahydrouridine (THU) (125 mg) minitablets, or matched placebo. Trial medication will be dispensed on Day 1 of each cycle and taken once weekly (Days 1, 8, 15, 22) for 24 weeks. Dosing of Dec+THU will follow weight-based dosing at 0.2mg/kg and 10mg/kg respectively. This is a phase II, multicenter, double-blind, placebo-controlled randomized trial | Drug | active drug |
| Matched Placebo (Capsules)Placebo capsules will be administered on the same schedule and dosing frequency to the active drug | Drug | matched placebo |
Primary outcome
Change in variant allele fraction (VAF) in peripheral blood mononuclear cells (PBMC) at the completion of 24 weeks of treatment.
Time frame: End of Treatment (Week 24)
Change in variant allele fraction (VAF) in peripheral blood mononuclear cells (PBMC), at the completion of 24 weeks of treatment, will be used to compare the evolution of clonal cytopenia of undetermined significance (CCUS) in individuals with CCUS and associated clinically significant cytopenia receiving Dec+THU compared with those receiving placebo, by intention-to-treat analysis. VAF will be assessed by capture sequencing using the Auckland Myeloid Gene Panel V4 (AMGPV4)
8 secondary outcomes
Number and proportion of participants: a) experiencing Grade 3, 4 and 5 adverse events (AE) b) discontinuing treatment due to AEs or Serious Adverse Events (SAEs) c) living with HIV maintaining HIV Viral Load (VL) suppression
Time frame: End of Treatment (Week 24)
Number and proportion of participants completing planned 24 weeks of treatment.
Time frame: End of Treatment (Week 24)
Number and proportion of participants with cytopenia response
Time frame: End of Treatment (Week 24) and Follow Up 1 (Week 48)
Duration of cytopenia response
Time frame: End of Treatment (Week 24) and Follow Up Visit 1 (Week 48)
Changes in VAF in subgroups defined by cytopenias and baseline mutations
Time frame: Baseline (Week 0), at the start of Cycle 4 Day 1 (Week 12) (each cycle is 28 days), End of Treatment (Week 24), Follow Up Visit 1 (Week 48) and Follow Up Visit 2 (Week 96)
Changes in peripheral blood VAF
Time frame: Baseline (Week 0), at the start of Cycle 4 Day 1 (Week 12) (each cycle is 28 days), End of Treatment (Week 24), Follow Up Visit 1 (Week 48), Follow Up Visit 2 (Week 96)
Changes in the levels of inflammatory cytokines between treatment groups in peripheral blood and bone marrow.
Time frame: Baseline (Week 0), at the start of Cycle 4 Day 1 (Week 12) (each cycle is 24 weeks), End of Treatment (Week 24), Follow Up Visit 1 (Week 48), Follow Up Visit 2 (Week 96)
Changes in bone marrow (BM) VAF
Time frame: Screening, End of Treatment (Week 24)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Oral Decitabine and Tetrahydrouridine in people with Clonal Cytopenia of Uncertain Significance and CCUS Clonal Cytopenia of Undetermined Significance, run by Clinical Hub for Interventional Research (CHOIR) at 3 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Professor Mark Polizzotto (+61000000000, mosaic.jcsmr@anu.edu.au), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in variant allele fraction (VAF) in peripheral blood mononuclear cells (PBMC) at the completion of 24 weeks of treatment. (time frame: End of Treatment (Week 24)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.