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

NCT07710534 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MCC-26-23119
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Relapsed / Refractory AML; High Risk Myelodysplastic Syndrome; High Risk Myeloproliferative Neoplasms

Keywords

Relapsed / Refractory AML; High Risk Myelodysplastic Syndrome; High Risk Myeloproliferative Neoplasms

Outcome Measures

Primary Outcomes (1)

• Compare safety and tolerability of the arms

  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)

Secondary Outcomes (10)

• 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

  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

  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

  Baseline and end of Cycle 2, each cycle is 28 days.

• Estimate best response rates in acute myeloid leukemia (AML) for both arms

  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

  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.

Study Arms (2)

Arm A: Metronomic decitabine-cedazuridine (DEC-C) plus venetoclax (VEN)

EXPERIMENTAL

Drug: Decitabine-cedazuridine plus venetoclax (DEC-C+VEN)

Arm B: Azacitidine (AZA) plus venetoclax (VEN)

ACTIVE COMPARATOR

Drug: Azacitidine plus venetoclax (AZA+VEN)

Interventions

Azacitidine plus venetoclax (AZA+VEN) DRUG

Azacitidine (AZA) 75 milligrams per meters squared (mg/m2) taken per institutional practice, plus venetoclax (VEN) standard ramp-up

Arm B: Azacitidine (AZA) plus venetoclax (VEN)

Decitabine-cedazuridine plus venetoclax (DEC-C+VEN) DRUG

Decitabine-cedazuridine (DEC-C) dosage per protocol taken by mouth once weekly plus Venetoclax (VEN) 400 milligrams (mg), taken by mouth once weekly

Arm A: Metronomic decitabine-cedazuridine (DEC-C) plus venetoclax (VEN)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Virginia Commonwealth University: lead

Study Sites (1)

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

decitabine and cedazuridine drug combination; venetoclax; Azacitidine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Keri Maher, DO

  Virginia Commonwealth University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Massey IIT Research Operations

CONTACT

804-628-6430; masseyepd@vcu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2026
• First Posted: July 17, 2026
• Study Start (Estimated): September 30, 2026
• Primary Completion (Estimated): September 30, 2031
• Study Completion (Estimated): December 31, 2033
• Last Updated: July 17, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)