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

2026년 7월 13일 업데이트: 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.

연구 개요

상태

아직 모집하지 않음

정황

개입 / 치료

상세 설명

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.

연구 유형

중재적

등록 (추정된)

40

단계

  • 2 단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

  • 이름: Massey IIT Research Operations
  • 전화번호: 804-628-6430
  • 이메일: masseyepd@vcu.edu

연구 장소

  • 미국
    • Virginia
      • Richmond, Virginia, 미국, 23298
        • Virginia Commonwealth University
        • 수석 연구원:
          • Keri Maher, DO
        • 연락하다:
          • Acute Leukemia/Myeloid Malignancies CTO Team
          • 전화번호: 804-628-6430
          • 이메일: masseyhiit@vcu.edu

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

설명

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)

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
실험적: Arm A: Metronomic decitabine-cedazuridine (DEC-C) plus venetoclax (VEN)
의약품: 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
활성 비교기: Arm B: Azacitidine (AZA) plus venetoclax (VEN)
의약품: Azacitidine plus venetoclax (AZA+VEN)
Azacitidine (AZA) 75 milligrams per meters squared (mg/m2) taken per institutional practice, plus venetoclax (VEN) standard ramp-up

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Compare safety and tolerability of the arms
기간: 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)

2차 결과 측정

결과 측정
측정값 설명
기간
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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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
기간: 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

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

Virginia Commonwealth University

수사관

  • 수석 연구원: Keri Maher, DO, Virginia Commonwealth University

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 9월 30일

기본 완료 (추정된)

2031년 9월 30일

연구 완료 (추정된)

2033년 12월 31일

연구 등록 날짜

최초 제출

2026년 7월 7일

QC 기준을 충족하는 최초 제출

2026년 7월 13일

처음 게시됨 (실제)

2026년 7월 17일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 7월 17일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 7월 13일

마지막으로 확인됨

2026년 7월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • MCC-26-23119

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

아니요

IPD 계획 설명

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

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

예

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다