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

13. juli 2026 oppdatert av: 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.

Studieoversikt

Status

Har ikke rekruttert ennå

Forhold

Intervensjon / Behandling

Detaljert beskrivelse

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.

Studietype

Intervensjonell

Registrering (Antatt)

40

Fase

  • Fase 2

Kontakter og plasseringer

Denne delen inneholder kontaktinformasjon for de som utfører studien, og informasjon om hvor denne studien blir utført.

Studiekontakt

  • Navn: Massey IIT Research Operations
  • Telefonnummer: 804-628-6430
  • E-post: masseyepd@vcu.edu

Studiesteder

  • Forente stater
    • Virginia
      • Richmond, Virginia, Forente stater, 23298
        • Virginia Commonwealth University
        • Hovedetterforsker:
          • Keri Maher, DO
        • Ta kontakt med:
          • Acute Leukemia/Myeloid Malignancies CTO Team
          • Telefonnummer: 804-628-6430
          • E-post: masseyhiit@vcu.edu

Deltakelseskriterier

Forskere ser etter personer som passer til en bestemt beskrivelse, kalt kvalifikasjonskriterier. Noen eksempler på disse kriteriene er en persons generelle helsetilstand eller tidligere behandlinger.

Kvalifikasjonskriterier

Alder som er kvalifisert for studier

  • Voksen
  • Eldre voksen

Tar imot friske frivillige

Nei

Beskrivelse

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)

Studieplan

Denne delen gir detaljer om studieplanen, inkludert hvordan studien er utformet og hva studien måler.

Hvordan er studiet utformet?

Designdetaljer

  • Primært formål: Behandling
  • Tildeling: Randomisert
  • Intervensjonsmodell: Parallell tildeling
  • Masking: Ingen (Open Label)

Våpen og intervensjoner

Deltakergruppe / Arm
Intervensjon / Behandling
Eksperimentell: Arm A: Metronomic decitabine-cedazuridine (DEC-C) plus venetoclax (VEN)
Legemiddel: 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
Aktiv komparator: Arm B: Azacitidine (AZA) plus venetoclax (VEN)
Legemiddel: Azacitidine plus venetoclax (AZA+VEN)
Azacitidine (AZA) 75 milligrams per meters squared (mg/m2) taken per institutional practice, plus venetoclax (VEN) standard ramp-up

Hva måler studien?

Primære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
Compare safety and tolerability of the arms
Tidsramme: 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)

Sekundære resultatmål

Resultatmål
Tiltaksbeskrivelse
Tidsramme
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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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
Tidsramme: 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

Samarbeidspartnere og etterforskere

Det er her du vil finne personer og organisasjoner som er involvert i denne studien.

Sponsor

Virginia Commonwealth University

Etterforskere

  • Hovedetterforsker: Keri Maher, DO, Virginia Commonwealth University

Studierekorddatoer

Disse datoene sporer fremdriften for innsending av studieposter og sammendragsresultater til ClinicalTrials.gov. Studieposter og rapporterte resultater gjennomgås av National Library of Medicine (NLM) for å sikre at de oppfyller spesifikke kvalitetskontrollstandarder før de legges ut på det offentlige nettstedet.

Studer hoveddatoer

Studiestart (Antatt)

30. september 2026

Primær fullføring (Antatt)

30. september 2031

Studiet fullført (Antatt)

31. desember 2033

Datoer for studieregistrering

Først innsendt

7. juli 2026

Først innsendt som oppfylte QC-kriteriene

13. juli 2026

Først lagt ut (Faktiske)

17. juli 2026

Oppdateringer av studieposter

Sist oppdatering lagt ut (Faktiske)

17. juli 2026

Siste oppdatering sendt inn som oppfylte QC-kriteriene

13. juli 2026

Sist bekreftet

1. juli 2026

Mer informasjon

Begreper knyttet til denne studien

Nøkkelord

Ytterligere relevante MeSH-vilkår

Andre studie-ID-numre

  • MCC-26-23119

Plan for individuelle deltakerdata (IPD)

Planlegger du å dele individuelle deltakerdata (IPD)?

NEI

IPD-planbeskrivelse

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

Legemiddel- og utstyrsinformasjon, studiedokumenter

Studerer et amerikansk FDA-regulert medikamentprodukt

Ja

Studerer et amerikansk FDA-regulert enhetsprodukt

Nei

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