Recruiting
Phase 2

Observational Study

Sponsor:

Virginia Commonwealth University

Code:

NCT07710534

Conditions

Relapsed / Refractory AML

High Risk Myelodysplastic Syndrome

High Risk Myeloproliferative Neoplasms

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

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

Azacitidine plus venetoclax (AZA+VEN)

Study Details

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

Study ID

NCT07710534

Start date

Sep 16, 2026

Status verified date

Sep, 2026

Completion date

Dec 31, 2033

Anticipated

Primary completion date

Sep 30, 2031

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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)

Study Design

Enrollment

40 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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

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

Interventions

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

Azacitidine plus venetoclax (AZA+VEN)

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

Primary outcome measure

  • Compare safety and tolerability of the arms [ Time Frame: 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) ]

Central Contacts and Locations

Central contacts

Massey IIT Research Operations

804-628-6430masseyepd@vcu.edu

Locations

Virginia Commonwealth University

Recruiting

Richmond, Virginia, United States, 23298

Contacts

Acute Leukemia/Myeloid Malignancies CTO Team

804-628-6430masseyhiit@vcu.edu

Principal Investigator:

Keri Maher, DO

More Information

Sponsor

Virginia Commonwealth University

Last update posted

Sep 21, 2026

Last verified

Sep, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-24. This information was provided to ClinicalTrials.gov by Virginia Commonwealth University on 2026-09-21. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.