Venetoclax and Bomedemstat in Patients With Relapsed/Refractory Acute Myeloid Leukemia

NCT05597306 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 20220733NCI-2022-09456
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Acute Myeloid Leukemia, in Relapse; Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (2)

• 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.

  Up to 72 weeks

• 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.

  Up to 72 weeks

Secondary Outcomes (2)

• Overall Response Rate (ORR)

  Up to 72 weeks

• Proportion of Participants with Measurable Residual Disease

  Up to 72 weeks

Study Arms (2)

Part 1: VenBom Dose Escalation/De-Escalation Cohort

EXPERIMENTAL

Participants in this group will receive Venetoclax and Bomedemstat (VenBom) in a dose escalation/de-escalation design to determine the maximum tolerated dose (MTD). Participants will receive VenBom for 21 days on (Days 1-21) and seven days off (Days 22-28) during a 28-day cycle for three months. Doses will be administered as follows: * Dose Level -2: 0.375 mg/kg daily (d) Bomedemstat and 200 mg/d Venetoclax; * Dose Level -1: 0.75 mg/kg/d Bomedemstat and 200 mg/d Venetoclax; * Dose Level 1 (Starting): 1.5 mg/kg/d Bomedemstat and 200 mg/d Venetoclax; * Dose Level 2: 3 mg/kg/d Bomedemstat and 200 mg/d Venetoclax; * Dose Level 3: 3 mg/kg/d Bomedemstat and 400 mg/d Venetoclax. Participants will receive three cycles of VenBom, but may continue to receive treatment as long as receiving clinical benefit or until disease progression. Participants starting at dose levels -2, -1, or 1 receive 100 mg Venetoclax on Cycle 1 Day 1.

Drug: Bomedemstat; Drug: Venetoclax

Part 2: VenBom Expansion Cohort

EXPERIMENTAL

Participants in this group will receive VenBom therapy at the most appropriate dose determined in Part 1. Participants will continue to receive treatment as long as receiving clinical benefit or until disease progression.

Drug: Bomedemstat; Drug: Venetoclax

Interventions

Bomedemstat DRUG

Bomedemstat will be administered orally once daily via capsule.

Also known as: IMG-7289

Part 1: VenBom Dose Escalation/De-Escalation Cohort; Part 2: VenBom Expansion Cohort

Venetoclax DRUG

Venetoclax will be administered orally once daily via tablet.

Also known as: Venclexta

Part 1: VenBom Dose Escalation/De-Escalation Cohort; Part 2: VenBom Expansion Cohort

Eligibility Criteria

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

You may qualify if:

• A. Confirmed diagnosis of one of the following:
• \. Relapsed/refractory Acute Myeloid Leukemia (AML) following failure of at least one standard, front-line therapy. Patients must have an AML diagnosis per the World Health Organization (WHO) criteria, regardless of etiology, sub-type or treatment history.
• B. Adult male or female patients 18 years of age or older.
• C. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 (Appendix A: Performance Status Scales).
• D. Patients must satisfy the following laboratory criteria:
• 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.
• White blood cell (WBC) count \< 25,000 cells/μL before administration of VenBom on Cycle 1 Day 1. Note: During Cycle 1 only, hydroxyurea may be used to control the level of circulating leukemic blast cell counts to not lower than 10,000 cells/μL.
• Platelet count ≥ 20,000 cells/μL before administration of VenBom on Cycle 1 Day 1. Note: Transfusions permitted to achieve this threshold.
• E. Suitable venous access to allow for all study related-blood sampling (safety and research).
• F. Estimated life expectancy, in the judgment of the Investigator, that will permit receipt of at least 3 months of treatment.
• G. Voluntary written consent must be given before performance of any study-related procedure not part of standard medical care with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care or other benefits to which they are entitled to receive.
• H. Female patients who:

You may not qualify if:

• A. Treatment with clinically significant metabolic enzyme inducers within 14 days before the first dose of the study drug. (Refer to Section 6.3 for instruction on use of strong or moderate Cytochrome P450 (CYP3A) inhibitors/inducers.)
• B. Diagnosis of acute promyelocytic leukemia (APL)
• C. Therapy with any investigational products, anti-neoplastic therapy, or radiotherapy within 14 days prior to Cycle 1, Day 1. Exception: Patients actively receiving hydroxyurea are eligible and may continue to receive hydroxyurea to control the level of circulating leukemic blast counts to not lower than 10,000 cells/μL during Cycle 1 of protocol treatment.
• D. Candidates for standard and/or potentially curative treatments (a candidate is defined as a patient that is both eligible and willing to have these treatments).
• E. Major surgery within 14 days before the first dose of study drug or a scheduled surgery during the study period.
• F. Grade 2 or higher diarrhea as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 despite optimal anti-diarrheal supportive care within 7 days prior to Cycle 1, Day 1.
• G. Known cardiopulmonary disease defined as one of the following:
• 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).
• Known moderate to severe chronic obstructive pulmonary disease (COPD), interstitial lung disease, and pulmonary fibrosis.
• H. Active uncontrolled infection or severe infectious disease, such as severe pneumonia, meningitis, or septicemia.
• I. Uncontrolled human immunodeficiency virus (HIV), defined as dateable viral load.
• J. Known hepatitis B surface antigen seropositive. (Note: Patients who have isolated positive hepatitis B core antibody (i.e., in the setting of negative hepatitis B surface antigen and negative hepatitis B surface antibody) must have an undetectable hepatitis B viral load if they are to participate in this study.)

Sponsors & Collaborators

• Terrence J Bradley, MD: lead
• Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA): collaborator

Study Sites (1)

University of Miami

Miami, Florida, 33136, United States

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

bomedemstat; venetoclax

Condition Hierarchy (Ancestors)

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

Study Officials

• Terrence J Bradley, MD

  University of Miami

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alessia Zoso, PhD

CONTACT

305-243-2373; azoso@med.miami.edu

Terrence J Bradley, MD

CONTACT

305-243-1000; tbradley@med.miami.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Clinical

Model Details: Phase 1 dose escalation/de-escalation and dose expansion design.

Study Record Dates

• First Submitted: October 24, 2022
• First Posted: October 28, 2022
• Study Start: November 19, 2022
• Primary Completion (Estimated): November 19, 2026
• Study Completion (Estimated): November 19, 2026
• Last Updated: January 8, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)