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Trial Radar IA
Lo studio clinico NCT07435636 (MOSAIC) per Clonal Cytopenia of Uncertain Significance, CCUS Citopenia clonale di significato indeterminato, Ematopoiesi clonale è non ancora in arruolamento. Consulti la vista a schede del Radar degli Studi Clinici e gli strumenti di scoperta IA per tutti i dettagli. Oppure, ponga pure una domanda qui.
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Modulation of Stem Cell Differentiation in Individuals With High Risk Clonal Haematopoiesis (MOSAIC) Fase II 80 Randomizzato Doppio cieco Controllato con placebo Innovativo

Non ancora in arruolamento
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La sperimentazione clinica NCT07435636 (MOSAIC) è uno studio interventistico di Fase II volto a esaminare il trattamento per Clonal Cytopenia of Uncertain Significance, CCUS Citopenia clonale di significato indeterminato, Ematopoiesi clonale, attualmente non ancora in arruolamento. L'arruolamento dovrebbe iniziare il 13 aprile 2026, con l'obiettivo di raggiungere 80 partecipanti. Sotto la guida di Clinical Hub for Interventional Research (CHOIR), dovrebbe concludersi entro il 1 ottobre 2030. I dati più recenti da ClinicalTrials.gov sono stati aggiornati l'ultima volta il 27 febbraio 2026.
Sommario breve
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...

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Titolo ufficiale

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

Patologie
Clonal Cytopenia of Uncertain SignificanceCCUS Citopenia clonale di significato indeterminatoEmatopoiesi clonale
Altri ID dello studio
  • MOSAIC
  • 24-CH-002
Numero NCT
NCT07435636
Data di inizio (effettiva)
2026-04-13
Ultimo aggiornamento pubblicato
2026-02-27
Data di completamento (stimata)
2030-10
Arruolamento (previsto)
80
Tipo di studio
Interventistico
FASE
Fase II
Stato
Non ancora in arruolamento
Parole chiave
MOSAIC
CH
Modulation of stem cell differentiation
CCUS
persistent cytopenia
clonal hematopoiesis
clonal haematopoiesis
Clonal Cytopenia of Uncertain Significance
Scopo principale
Trattamento
Allocazione
Randomizzato
Modello di intervento
In parallelo
Mascheramento
Quadruplo
Bracci / Interventi
Gruppo/Braccio di partecipantiIntervento/Trattamento
Sperimentaleactive drug
Oral combination capsules containing both decitabine and tetrahydrouridine (Dec+THU)
Oral Decitabine and Tetrahydrouridine
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, doubl...Mostra di più
Comparatore placebomatched placebo
Matched Placebo (Capsules)
Placebo capsules will be administered on the same schedule and dosing frequency to the active drug
Esito primario
Misure di esitoDescrizione della misuraArco temporale
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)
End of Treatment (Week 24)
Esito secondario
Misure di esitoDescrizione della misuraArco temporale
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.
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
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
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
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.
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.
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.
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.
Screening, End of Treatment (Week 24)
Assistente alla partecipazione
Criteri di eleggibilità

Età idonea
Adulto, Adulto anziano
Età minima
60 Years
Sessi idonei
Tutti

  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

  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

Clinical Hub for Interventional Research (CHOIR) logoClinical Hub for Interventional Research (CHOIR)
Contatti principali dello studio
Contatto: Professor Mark Polizzotto, +61000000000, [email protected]
3 Centri dello studio in 1 paesi

Australian Capital Territory

Canberra Health Services, Canberra, Australian Capital Territory, 2605, Australia
Professor Mark Polizzotto, Contatto, +61000000000, [email protected]

New South Wales

Prince of Wales Hospital, Randwick, New South Wales, 2031, Australia
Dr Annmarie Bosco, Contatto, +61000000000
Westmead Hospital, Westmead, New South Wales, 2145, Australia
Dr Lachlin Vaughan, Contatto, +61000000000