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Metronomic Decitabine-Cedazuridine and Venetoclax in R/R AML, HR-MDS, HR/AP MPN

13 июля 2026 г. обновлено: Virginia Commonwealth University

Metronomic Decitabine-Cedazuridine and Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia R/R AML), High Risk Myelodysplastic Syndrome (HR-MDS), and High-Risk Myeloproliferative Neoplasms (HR/AP MPN)

This is a single-center randomized phase 2 open-label clinical trial.

Обзор исследования

Статус

Еще не набирают

Условия

Вмешательство/лечение

Подробное описание

Patients are randomized 1:1 to metronomic-dosed Decitabine-Cedazuridine and Venetoclax (DEC-C+VEN) vs (Azacitidine (AZA)+ Venetoclax (VEN). Patients will be stratified at randomization based on disease cohort Relapsed/Refractory Acute Myeloid Leukemia (R/R AML), High Risk Myelodysplastic Syndrome (HR-MDS), High Risk Myeloproliferative Neoplasms (HR/AP-MPN) Patients will undergo treatment indefinitely until progression, unacceptable toxicity, or allogeneic hematopoietic transplant.

Тип исследования

Интервенционный

Регистрация (Оцененный)

40

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: Massey IIT Research Operations
  • Номер телефона: 804-628-6430
  • Электронная почта: masseyepd@vcu.edu

Места учебы

  • Соединенные Штаты
    • Virginia
      • Richmond, Virginia, Соединенные Штаты, 23298
        • Virginia Commonwealth University
        • Главный следователь:
          • Keri Maher, DO
        • Контакт:
          • Acute Leukemia/Myeloid Malignancies CTO Team
          • Номер телефона: 804-628-6430
          • Электронная почта: masseyhiit@vcu.edu

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

  • Взрослый
  • Пожилой взрослый

Принимает здоровых добровольцев

Нет

Описание

Inclusion Criteria:

  • Age ≥18 years at time of enrollment

  • Diagnosis of one of the following by World Health Organization (WHO) International Consensus Classification (ICC) criteria as determined by local assessment:

    • Relapsed/ refractory acute myeloid leukemia (R/R AML) as defined by ≥5% marrow blasts or unequivocal, measurable extramedullary disease
    • High Risk Myelodysplastic Syndrome (HR-MDS) (high/very high risk MDS by Revised International Prognostic Scoring System (IPSS-R) or Molecular International Prognostic Scoring System (IPSS-M)
    • high-risk accelerated-phase myeloproliferative neoplasm (HR/AP-MPN) defined by ≥10% blasts in blood or bone marrow
  • Eastern Cooperative Oncology Group (ECOG) Performance status 0-3
  • White blood cell (WBC) count ≤25 × 109/Liter (L) (cytoreduction with hydroxyurea or steroids is allowed to achieve this)
  • Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) ≤3 × upper limit of normal (ULN) (≤5 × ULN if due to leukemic involvement)
  • Total bilirubin ≤2 × ULN (unless the elevation is due to Gilbert's or hemolysis)
  • Creatinine clearance ≥ 30 milliliters / minute (mL/min)
  • Women of child-bearing potential must not be pregnant or breastfeeding and must have a negative pregnancy test at screening. Women of non-childbearing potential are those who have had a hysterectomy or bilateral oophorectomy, or who have completed menopause (no menses for at least one year and age ≥65 or follicle-stimulating hormone levels in the menopausal range).
  • Subjects and their partners with reproductive potential must agree to use effective contraceptive measures during the study and for 3 months after the last dose of study treatment. Effective contraception includes methods such as oral contraceptives or double-barrier method.

Exclusion Criteria:

  • Prior use of hypomethylating agent and venetoclax in combination (Note, use of hypomethylating agent and/or venetoclax separately in alternative combinations with other drugs is allowed)
  • Inability to tolerate oral therapies, or medical co-morbidities that significantly impact parenteral absorption
  • Acute promyelocytic leukemia myeloproliferative neoplasm (MPN) with the Philadelphia chromosome translocation (BCR:ABL) translocation
  • Clinically significant cardiovascular disease as defined by unstable angina
  • New York Heart Association class III/IV congestive heart failure
  • Treatment with any investigational drug or therapy within 2 weeks of study treatment or 5 half-lives before the first dose of study treatment, whichever is shorter
  • Known hypersensitivity to azacitidine, venetoclax, decitabine or cedazuridine
  • Cytotoxic chemotherapy or prior azacitidine or decitabine within 2 weeks of first dose of study treatment
  • Concurrent use of AML/MDS/MPN therapies including lenalidomide, erythropoietin, luspatercept, cytotoxic chemotherapies, targeted agents, etc Note: hydroxyurea is allowed in Cycle 1 if necessary for cytoreduction and/or cytarabine not exceeding a maximum dose of 1 gram per meter squared (g/m2) in Cycle 1 is also allowed for cytoreduction
  • Uncontrolled intercurrent illness or infection (those with controlled HIV, hepatitis, or other chronic infections are eligible)
  • Untreated central nervous system disease
  • Pregnancy or breastfeeding
  • Other active malignancy requiring systemic therapy during duration of trial or otherwise would confound endpoints (eg, second malignancy present where survival is expected to be less than 6 months)

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: Нет (открытая этикетка)

Оружие и интервенции

Группа участников / Армия
Вмешательство/лечение
Экспериментальный: Arm A: Metronomic decitabine-cedazuridine (DEC-C) plus venetoclax (VEN)
Лекарство: Decitabine-cedazuridine plus venetoclax (DEC-C+VEN)
Decitabine-cedazuridine (DEC-C) dosage per protocol taken by mouth once weekly plus Venetoclax (VEN) 400 milligrams (mg), taken by mouth once weekly
Активный компаратор: Arm B: Azacitidine (AZA) plus venetoclax (VEN)
Лекарство: Azacitidine plus venetoclax (AZA+VEN)
Azacitidine (AZA) 75 milligrams per meters squared (mg/m2) taken per institutional practice, plus venetoclax (VEN) standard ramp-up

Что измеряет исследование?

Первичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Compare safety and tolerability of the arms
Временное ограничение: Baseline through 30 days following last dose of protocol treatment, indefinitely until progression, unacceptable toxicity, or allogeneic hematopoietic transplant, whichever comes first, assessed up to 10 years)
Incidence of Grade 3 or greater treatment related adverse events per the National Cancer Institute's (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 6.0 Treatment-related hematologic toxicity will be defined as a worsening from baseline CTCAE grade accompanied by clinically significant consequences, including new transfusion requirement, clinically significant bleeding, hospitalization, dose interruption/reduction, growth factor support, or investigator determination of clinically significant change from baseline
Baseline through 30 days following last dose of protocol treatment, indefinitely until progression, unacceptable toxicity, or allogeneic hematopoietic transplant, whichever comes first, assessed up to 10 years)

Вторичные показатели результатов

Мера результата
Мера Описание
Временное ограничение
Characterize events of special interest defined as Grade 3 or greater adverse events (AEs) with attention to prolonged cytopenias, febrile neutropenia, serious infection, and serious bleeding events for both arms
Временное ограничение: Baseline through 30 days following last dose of protocol treatment, indefinitely until progression, unacceptable toxicity, or allogeneic hematopoietic transplant, whichever comes first, assessed up to 10 years.
Incidence of prolonged cytopenias defined as absolute neutrophil count (ANC) ≤ 500/microliter (µL) and/or platelets ≤ 50,000/µL for greater than 28 days and febrile neutropenia, serious infection (requiring intravenous (IV) antibiotics or hospitalization) or serious bleeding events (requiring hospitalization or procedural intervention)
Baseline through 30 days following last dose of protocol treatment, indefinitely until progression, unacceptable toxicity, or allogeneic hematopoietic transplant, whichever comes first, assessed up to 10 years.
Estimate the event free survival (EFS) for both arms
Временное ограничение: Day 1 of protocol treatment up to 2 years following last dose of treatment
Event free survival (EFS) defined as time from treatment initiation to relapse, disease progression, or death from any cause
Day 1 of protocol treatment up to 2 years following last dose of treatment
Estimate minimal residual disease (MRD) negativity rates in acute myeloid leukemia (AML) for both arms
Временное ограничение: Baseline and end of Cycle 2, each cycle is 28 days.
Minimal residual disease (MRD) negativity defined as <0.1% by multiparameter flow cytometry or next generation sequencing (NGS)-based MRD negativity when available (below assay-specific detection threshold). Multiparameter flow cytometry or NGS-MRD analyzes patient's genetic material, deoxyribonucleic acid (DNA), from bone marrow or peripheral blood to detect patient-specific genetic sequences associated with cancer cells.
Baseline and end of Cycle 2, each cycle is 28 days.
Estimate best response rates in acute myeloid leukemia (AML) for both arms
Временное ограничение: Baseline, Cycle 2 Day 28, Cycle 4 Day 28, If patient has not reached maximum response by Cycle 4 Day 28 biopsy, an additional biopsy will be performed at Cycle 7 Day 28, or at disease progression, whichever comes first, assessed up to 7 months.
Best response defined as <0.1% by multiparameter flow cytometry or next generation sequencing (NGS) based MRD negativity when available (below assay-specific detection threshold)
Baseline, Cycle 2 Day 28, Cycle 4 Day 28, If patient has not reached maximum response by Cycle 4 Day 28 biopsy, an additional biopsy will be performed at Cycle 7 Day 28, or at disease progression, whichever comes first, assessed up to 7 months.
Estimate duration of response (DoR) for both arms
Временное ограничение: Start of protocol treatment through up to 2 years following last dose of protocol treatment. Patients will undergo treatment indefinitely until progression, unacceptable toxicity, or allogeneic hematopoietic transplant.
Duration of response (DoR) defined from first documented complete response (CR), or complete remission with incomplete hematologic recovery (CRi). CRi means that while the cancer is gone, the patient's blood cell counts have not yet returned to normal, or Morphologic Leukemia-Free State (MLFS). MLFS indicates the absence of detectable leukemic blasts to relapse or death.
Start of protocol treatment through up to 2 years following last dose of protocol treatment. Patients will undergo treatment indefinitely until progression, unacceptable toxicity, or allogeneic hematopoietic transplant.
Estimate overall survival (OS) for both arms
Временное ограничение: Start of protocol treatment through up to 2 years following last dose of protocol treatment. Patients will undergo treatment indefinitely until progression, unacceptable toxicity, or allogeneic hematopoietic transplant.
overall survival (OS) defined as time from treatment initiation to death from any cause.
Start of protocol treatment through up to 2 years following last dose of protocol treatment. Patients will undergo treatment indefinitely until progression, unacceptable toxicity, or allogeneic hematopoietic transplant.
Estimate of early mortality rate at 30 and 60 days in the relapsed or refractory acute myeloid leukemia (R/R AML) cohort for both arms
Временное ограничение: Day 30 and Day 60 after start of protocol treatment
A ssess short-term survival by the 30-day and 60-day mortality in the R/R AML cohort.
Day 30 and Day 60 after start of protocol treatment
Estimate health care utilization metrics for both arms
Временное ограничение: Cycles 1 through 4, about 112 days
Health care utilization metrics including the number of red blood cell (RBC) and platelet transfusions per patient in Cycles 1-4 (transfusion independence, defined as no transfusions for 4 and 8 consecutive weeks) and unplanned hospitalizations attributable to disease or treatment related complications.
Cycles 1 through 4, about 112 days
Estimate of quality of life (QoL) metrics for both arms
Временное ограничение: Cycle 3 Day 1 ± 1 week (each cycle is 28 days), and Cycle 5 Day 1 ± 1 week, or end of study treatment (± 2 weeks) if occurring prior to the four-month timepoint (when feasible)
Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ C30), a 30-item questionnaire to capture the subjective experiences of cancer patients, including physical, emotional, and social well-being. Items are scored on a 1-4 Likert scale (except global health status, scale 1-7) and scores are linearly transformed to a 0-100 scale, where higher scores on functional scales signal better functioning, higher scores on symptoms scales signal higher symptom burden, and higher scores on global health status signify better overall quality of life
Cycle 3 Day 1 ± 1 week (each cycle is 28 days), and Cycle 5 Day 1 ± 1 week, or end of study treatment (± 2 weeks) if occurring prior to the four-month timepoint (when feasible)
Estimate proportion of patients proceeding to allo-HCT for both arms
Временное ограничение: Start of treatment, up to 2 years following last dose of study treatment
Proportion of patients proceeding to allogeneic hematopoietic cell transplantation (allo-HCT)
Start of treatment, up to 2 years following last dose of study treatment

Соавторы и исследователи

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

Спонсор

Virginia Commonwealth University

Следователи

  • Главный следователь: Keri Maher, DO, Virginia Commonwealth University

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)

30 сентября 2026 г.

Первичное завершение (Оцененный)

30 сентября 2031 г.

Завершение исследования (Оцененный)

31 декабря 2033 г.

Даты регистрации исследования

Первый отправленный

7 июля 2026 г.

Впервые представлено, что соответствует критериям контроля качества

13 июля 2026 г.

Первый опубликованный (Действительный)

17 июля 2026 г.

Обновления учебных записей

Последнее опубликованное обновление (Действительный)

17 июля 2026 г.

Последнее отправленное обновление, отвечающее критериям контроля качества

13 июля 2026 г.

Последняя проверка

1 июля 2026 г.

Дополнительная информация

Термины, связанные с этим исследованием

Ключевые слова

Дополнительные соответствующие термины MeSH

Другие идентификационные номера исследования

  • MCC-26-23119

Планирование данных отдельных участников (IPD)

Планируете делиться данными об отдельных участниках (IPD)?

НЕТ

Описание плана IPD

There is no plan to share individual patient data. Datasets are available on reasonable request to the author.

Информация о лекарствах и устройствах, исследовательские документы

Изучает лекарственный продукт, регулируемый FDA США.

Да

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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