Venetoclax and Bomedemstat in Patients With Relapsed/Refractory Acute Myeloid Leukemia
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorTerrence J Bradley, MD
About this trial
This study aims to learn about the safety, tolerability, and different dose levels' safety profiles of Venetoclax and Bomedemstat (VenBom) combination therapy in participants with relapsed or refractory acute myeloid leukemia.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Total bilirubin ≤ 2 upper limit of normal (ULN) except in patients with Gilbert's syndrome. Patients with Gilbert's syndrome may enroll if direct bilirubin is ≤ 1.5 x ULN of the direct bilirubin.
Alanine aminotransferase (ALT) and aspartate transaminase (AST) must be ≤ 3 × ULN.
Calculated creatinine clearance > 50 ml/min.
Hemoglobin > 8 g/dL (prior red blood cell (RBC) transfusion allowed). Patients may be transfused to achieve this value. Elevated indirect bilirubin due to posttransfusion hemolysis is allowed.
Disqualifiers
Uncontrolled high blood pressure (i.e., systolic blood pressure > 180 mm Hg, diastolic blood pressure > 95 mm Hg)
Cardiomyopathy or history of ischemic heart disease. Exception: Patients with ischemic heart disease who have received treatment for acute coronary syndrome (ACS), myocardial infarction (MI), and/or coronary artery revascularization surgery (e.g., coronary artery bypass graft, stent) greater than 6 months before screening and who are without cardiac symptoms may enroll.
Congestive heart failure (New York Heart Association (NYHA) Class III or IV or Class II with a recent decompensation requiring hospitalization or referral to a heart failure clinic within 4 weeks before screening).
Moderate to severe aortic and/or mitral stenosis or other valvulopathy (ongoing).
Trial design
Design model
Sequential
Treatments tested in this trial
Bomedemstat
DrugBomedemstat will be administered orally once daily via capsule.
Venetoclax
DrugVenetoclax will be administered orally once daily via tablet.
Treatment groups
18 Participants
are divided into 2 treatment groupsGroup A: Part 1: VenBom Dose Escalation/De-Escalation CohortExperimental treatment 2 interventions
Group B: Part 2: VenBom Expansion CohortExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Incidence of Treatment-Emergent Toxicity
Toxicity is defined as including dose limiting toxicities (DLTs), serious adverse events (SAEs) and adverse events (AEs) in study participants. Toxicity will be assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, per physician discretion.
Time frame
Up to 72 weeks2
Recommended Phase 2 Dose (RP2D)
The RP2D of combination VenBom therapy will be determined as the maximum tolerated dose of study treatment as assessed by treating physician using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame
Up to 72 weeksSecondary outcomes
1
Overall Response Rate (ORR)
Rate of participants achieving complete response (CR), CR with incomplete neutrophil or platelet recovery (CRi), CR with incomplete hematologic recovery (CRh), partial remission (PR), or morphologic leukemia free state (MLFS) response to study treatment. Response will be assessed by treating physician using the modified 2017 European LeukemiaNet (ELN) AML Response Criteria.
Time frame
Up to 72 weeks2
Proportion of Participants with Measurable Residual Disease
Proportion of patients with measurable residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) at each bone marrow aspirate collection.
Time frame
Up to 72 weeksSponsors and contacts
Click on the lead sponsor to view all of their trials.
Terrence J Bradley, MD
Lead sponsor
University of Miami
Sponsor institution
Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)
Collaborator
Source ClinicalTrials.gov