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

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join 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 cannot join 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)

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

decitabine and cedazuridine. An orally available fixed-dose combination agent containing cedazuridine, a cytidine deaminase (CDA) inhibitor, and the cytidine antimetabolite decitabine, with potential antineoplastic activity. Upon oral administration of tdecitabine and cedazuridine, cedazuridine binds to and inhibits CDA, an enzyme primarily found in the gastrointestinal (GI) tract and liver that catalyzes the deamination of cytidine and cytidine analogs. This prevents the breakdown of decitabine, increases its bioavailability and efficacy while decreasing GI toxicity due to the administration of lower doses of decitabine. Decitabine exerts its antineoplastic activity through the incorporation of its triphosphate form into DNA, which inhibits DNA methyltransferase and results in hypomethylation of DNA. This interferes with DNA replication and decreases tumor cell growth. NCI Drug Dictionary

venetoclax. An orally bioavailable, selective small molecule inhibitor of the anti-apoptotic protein Bcl-2, with potential antineoplastic activity. Venetoclax mimics BH3-only proteins, the native ligands of Bcl-2 and apoptosis activators, by binding to the hydrophobic groove of Bcl-2 proteins thereby repressing Bcl-2 activity and restoring apoptotic processes in tumor cells. Bcl-2 protein is overexpressed in some cancers and plays an important role in the regulation of apoptosis; its expression is associated with increased drug resistance and tumor cell survival. Compared to the Bcl-2 inhibitor navitoclax, this agent does not inhibit bcl-XL and does not cause bcl-XL-mediated thrombocytopenia. NCI Drug Dictionary

Treatments listed in the registry

• 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
• 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

Randomized · Parallel · masking: None

Main goals

• Compare safety and tolerability of the 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))

Other goals

• 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
• Estimate the event free survival (EFS) for both arms
• Estimate minimal residual disease (MRD) negativity rates in acute myeloid leukemia (AML) for both arms
• Estimate best response rates in acute myeloid leukemia (AML) for both arms
• Estimate duration of response (DoR) for both arms
• Estimate overall survival (OS) for both arms
• 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
• Estimate health care utilization metrics for both arms
• Estimate of quality of life (QoL) metrics for both arms
• Estimate proportion of patients proceeding to allo-HCT for both arms

Planned enrollment: 40 (estimated).

• Virginia Commonwealth University, Richmond, Virginia

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT07710534
• NCI Drug Dictionary: C115102
• NCI Drug Dictionary: C103147

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Sep 20, 2026. Public record; not medical advice.