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对高风险克隆性造血个体干细胞分化的调节 (MOSAIC)

2026年11月2日 更新者：Clinical Hub for Interventional Research (CHOIR)

一项多中心、双盲、安慰剂对照的随机II期试验，旨在评估低剂量地西他滨与四氢尿苷对高危克隆性造血个体的疗效

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.

研究概览

地位

尚未招聘

条件

干预/治疗

研究类型

介入性

注册 (估计的)

80

阶段

  • 阶段2

联系人和位置

本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。

学习联系方式

学习地点

  • 澳大利亚
    • Australian Capital Territory
      • Canberra、Australian Capital Territory、澳大利亚、2605
        • Canberra Health Services
        • 接触：
    • New South Wales
      • Randwick、New South Wales、澳大利亚、2031
        • Prince of Wales Hospital
        • 接触：
          • Dr Annmarie Bosco
          • 电话号码：+61000000000
      • Westmead、New South Wales、澳大利亚、2145
        • Westmead Hospital
        • 接触：
          • Dr Lachlin Vaughan
          • 电话号码：+61000000000

参与标准

研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。

资格标准

适合学习的年龄

60年 至 85年 (成人、年长者)

接受健康志愿者

不

有资格学习的性别

全部

描述

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

学习计划

本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。

研究是如何设计的？

设计细节

  • 主要用途：治疗
  • 分配：随机化
  • 介入模型：并行分配
  • 屏蔽：四人间

武器和干预

参与者组/臂
干预/治疗
安慰剂比较：匹配的安慰剂
药品：Matched Placebo (Capsules)

Placebo capsules will be administered on the same schedule and dosing frequency to the active drug
实验性的：active drug

Oral combination capsules containing both decitabine and tetrahydrouridine (Dec+THU)
药品：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, double-blind, placebo-controlled randomized trial

研究衡量的是什么？

主要结果指标

结果测量
措施说明
大体时间
Change in variant allele fraction (VAF) in peripheral blood mononuclear cells (PBMC) at the completion of 24 weeks of treatment.
大体时间：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)
End of Treatment (Week 24)

次要结果测量

结果测量
措施说明
大体时间
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
大体时间：End of Treatment (Week 24)

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.
大体时间：End of Treatment (Week 24)

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
大体时间：End of Treatment (Week 24) and Follow Up 1 (Week 48)

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
大体时间：End of Treatment (Week 24) and Follow Up Visit 1 (Week 48)

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
大体时间：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)

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
大体时间：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)

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.
大体时间：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)

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
大体时间：Screening, End of Treatment (Week 24)

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)

合作者和调查者

在这里您可以找到参与这项研究的人员和组织。

赞助

Clinical Hub for Interventional Research (CHOIR)

合作者

The University of New South Wales
Australian National University
University of Auckland, New Zealand
Medical Research Future Fund
Treebough Therapies

研究记录日期

这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。

研究主要日期

学习开始 (估计的)

2026年12月1日

初级完成 (估计的)

2030年12月1日

研究完成 (估计的)

2030年12月1日

研究注册日期

首次提交

2026年2月17日

首先提交符合 QC 标准的

2026年2月23日

首次发布 (实际的)

2026年2月27日

研究记录更新

最后更新发布 (实际的)

2026年11月4日

上次提交的符合 QC 标准的更新

2026年11月2日

最后验证

2026年11月1日

更多信息

与本研究相关的术语

关键字

其他相关的 MeSH 术语

其他研究编号

  • 24-CH-002

药物和器械信息、研究文件

研究美国 FDA 监管的药品

不

研究美国 FDA 监管的设备产品

不

此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.

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