This is a single-center randomized phase 2 open-label clinical trial.
Age ≥18 years at time of enrollment
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
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
Parallel
Decitabine-cedazuridine plus venetoclax (DEC-C+VEN)
DrugDecitabine-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)
DrugAzacitidine (AZA) 75 milligrams per meters squared (mg/m2) taken per institutional practice, plus venetoclax (VEN) standard ramp-up
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
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
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)
Estimate the event free survival (EFS) for both arms
Event free survival (EFS) defined as time from treatment initiation to relapse, disease progression, or death from any cause
Estimate minimal residual disease (MRD) negativity rates in acute myeloid leukemia (AML) for both arms
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.
Estimate best response rates in acute myeloid leukemia (AML) for both arms
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)
Click on the lead sponsor to view all of their trials.
