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Модуляция дифференцировки стволовых клеток у лиц с высоким риском клонального гемопоэза (MOSAIC)

2 ноября 2026 г. обновлено: Clinical Hub for Interventional Research (CHOIR)

Многоцентровое, двойное слепое, плацебо-контролируемое рандомизированное исследование II фазы для оценки эффекта низких доз децитабина и тетрагидроуридина у лиц с высокорисковым клональным гемопоэзом

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.

Обзор исследования

Статус

Еще не набирают

Условия

Вмешательство/лечение

Тип исследования

Интервенционный

Регистрация (Оцененный)

80

Фаза

  • Фаза 2

Контакты и местонахождение

В этом разделе приведены контактные данные лиц, проводящих исследование, и информация о том, где проводится это исследование.

Контакты исследования

  • Имя: Professor Mark Polizzotto
  • Номер телефона: +61000000000
  • Электронная почта: mosaic.jcsmr@anu.edu.au

Места учебы

  • Австралия
    • Australian Capital Territory
      • Canberra, Australian Capital Territory, Австралия, 2605
        • Canberra Health Services
        • Контакт:
          • Professor Mark Polizzotto
          • Номер телефона: +61000000000
          • Электронная почта: mosaic.jcsmr@anu.edu.au
    • New South Wales
      • Randwick, New South Wales, Австралия, 2031
        • Prince of Wales Hospital
        • Контакт:
          • Dr Annmarie Bosco
          • Номер телефона: +61000000000
      • Westmead, New South Wales, Австралия, 2145
        • Westmead Hospital
        • Контакт:
          • Dr Lachlin Vaughan
          • Номер телефона: +61000000000

Критерии участия

Исследователи ищут людей, которые соответствуют определенному описанию, называемому критериям приемлемости. Некоторыми примерами этих критериев являются общее состояние здоровья человека или предшествующее лечение.

Критерии приемлемости

Возраст, подходящий для обучения

От 60 лет до 85 лет (Взрослый, Пожилой взрослый)

Принимает здоровых добровольцев

Нет

Полы, имеющие право на обучение

Все

Описание

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

Учебный план

В этом разделе представлена ​​подробная информация о плане исследования, в том числе о том, как планируется исследование и что оно измеряет.

Как устроено исследование?

Детали дизайна

  • Основная цель: Уход
  • Распределение: Рандомизированный
  • Интервенционная модель: Параллельное назначение
  • Маскировка: Четырехместный

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Плацебо Компаратор: соответствующее плацебо
Лекарство: Matched Placebo (Capsules)

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

Oral combination capsules containing both decitabine and tetrahydrouridine (Dec+THU)
Лекарство: 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

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Change in variant allele fraction (VAF) in peripheral blood mononuclear cells (PBMC) at the completion of 24 weeks of treatment.
Временное ограничение: 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)

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
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
Временное ограничение: 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.
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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
Временное ограничение: 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.
Временное ограничение: 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
Временное ограничение: 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)

Соавторы и исследователи

Здесь вы найдете людей и организации, участвующие в этом исследовании.

Спонсор

Clinical Hub for Interventional Research (CHOIR)

Соавторы

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

Даты записи исследования

Эти даты отслеживают ход отправки отчетов об исследованиях и сводных результатов на сайт ClinicalTrials.gov. Записи исследований и сообщаемые результаты проверяются Национальной медицинской библиотекой (NLM), чтобы убедиться, что они соответствуют определенным стандартам контроля качества, прежде чем публиковать их на общедоступном веб-сайте.

Изучение основных дат

Начало исследования (Оцененный)

1 декабря 2026 г.

Первичное завершение (Оцененный)

1 декабря 2030 г.

Завершение исследования (Оцененный)

1 декабря 2030 г.

Даты регистрации исследования

Первый отправленный

17 февраля 2026 г.

Впервые представлено, что соответствует критериям контроля качества

23 февраля 2026 г.

Первый опубликованный (Действительный)

27 февраля 2026 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

4 ноября 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

2 ноября 2026 г.

Последняя проверка

1 ноября 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • 24-CH-002

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Нет

Изучает продукт устройства, регулируемый Управлением по санитарному надзору за качеством пищевых продуктов и медикаментов США.

Нет

Эта информация была получена непосредственно с веб-сайта clinicaltrials.gov без каких-либо изменений. Если у вас есть запросы на изменение, удаление или обновление сведений об исследовании, обращайтесь по адресу register@clinicaltrials.gov. Как только изменение будет реализовано на clinicaltrials.gov, оно будет автоматически обновлено и на нашем веб-сайте. .

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