A Study to Evaluate MK-0482 for Relapsed/Refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML) (MK-0482-002)

NCT05038800 | Terminated Phase 1 Results FDA Drug

• 5 other identifiers: 0482-002MK-0482-0022023-003740-27-00U1111-1287-52692022-003740-27
• Study Type: interventional
• Target: 13
• Locations: 3 countries
• Sites: 5

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and recommended Phase 2 dose (RP2D) of MK-0482. There are 2 parts of this study. Part 1 is a dose escalation which will follow an accelerated titration design (ATD) for participants with relapsed/refractory (R/R) AML or CMML. Part 2 is a dose expansion for participants with R/R AML.

Conditions

Relapsed or Refractory Acute Myeloid Leukemia; Relapsed or Refractory Chronic Myelomonocytic Leukemia

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants Who Experienced a Dose-Limiting Toxicity (DLT)

  DLTs were defined as any of the following assessed as treatment-related by investigator (with pre-specified exceptions): Grade (Gr) 4 non-hematologic toxicity; Gr 3 non-hematologic toxicity; Gr 3 or Gr 4 non-hematologic laboratory value if: clinically significant medical intervention was required to treat the participant, the abnormality led to hospitalization, the abnormality persisted for \>1 week, electrolyte imbalances that lasted \>48 hours despite optimal therapy, or the abnormality resulted in a drug-induced liver injury; Gr 4 neutropenia and/or thrombocytopenia lasting \>14 days; \>2 week-delay in starting Cycle 2 due to treatment-related toxicity; treatment-related toxicity resulting in treatment discontinuation during DLT evaluation period; missing \>25% of MK-0482 dose during DLT evaluation period resulting from treatment-related adverse event (AE); or Gr 5 toxicity. The percentage of participants that experienced a DLT was reported for each arm.

  Cycle 1 (up to 21 days)

• Number of Participants Who Experience at Least One Adverse Event (AE)

  An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experienced at least one AE was reported for each arm.

  Up to approximately 10 months

• Number of Participants Who Discontinued Study Treatment Due to an AE

  An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinued study treatment due to an AE was reported for each arm.

  Up to approximately 4 months

Secondary Outcomes (8)

• Maximum Concentration (Cmax) of MK-0482

  Cycle 1: Pre-dose and Days 1, 2, 4, 8, and 15 post-dose. Cycle=21 days.

• Minimum Concentration (Cmin) of MK-0482

  Cycle 1: Pre-dose and Days 1, 2, 4, 8, and 15 post-dose. Cycle=21 days.

• Area Under the Plasma Concentration-Time Curve From Time Zero to 21 Days (AUC0-21) of MK-0482

  Cycle 1: Pre-dose and Days 1, 2, 4, 8, and 15 post-dose. Cycle=21 days.

• Time to Maximum Concentration (Tmax) of MK-0482

  Cycle 1: Pre-dose and Days 1, 2, 4, 8, and 15 post-dose. Cycle=21 days.

• Plasma Elimination Terminal Half-life (t½) of MK-0482

  Cycle 1: Pre-dose and Days 1, 2, 4, 8, and 15 post-dose. Cycle=21 days.

Study Arms (5)

MK-0482 7.5 mg Q3W

EXPERIMENTAL

Participants will receive 7.5 mg of MK-0482 via intravenous (IV) infusion on Day 1 of each 21-day cycle (every 3 weeks \[Q3W\]) for up to 35 cycles (approximately 24 months).

Biological: MK-0482

MK-0482 25 mg Q3W

EXPERIMENTAL

Participants will receive 25 mg of MK-0482 via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 24 months).

Biological: MK-0482

MK-0482 75 mg Q3W

EXPERIMENTAL

Participants will receive 75 mg of MK-0482 via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 24 months).

Biological: MK-0482

MK-0482 225 mg Q3W

EXPERIMENTAL

Participants will receive 225 mg of MK-0482 via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 24 months).

Biological: MK-0482

MK-0482 750 mg Q3W

EXPERIMENTAL

Participants will receive 750 mg of MK-0482 via IV infusion on Day 1 of each 21-day cycle (Q3W) for up to 35 cycles (approximately 24 months).

Biological: MK-0482

Interventions

MK-0482 BIOLOGICAL

IV infusion

MK-0482 225 mg Q3W; MK-0482 25 mg Q3W; MK-0482 7.5 mg Q3W; MK-0482 75 mg Q3W; MK-0482 750 mg Q3W

Eligibility Criteria

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

You may qualify if:

• Has confirmed diagnosis of AML with myelomonocytic or monoblastic/monocytic differentiation per World Health Organization (WHO) 2016 criteria and with confirmed refractory or relapsed disease (i.e., ≥5% blast in bone marrow or in peripheral blood) after treatment with available therapies known to benefit participant's AML subtypes or has a known diagnosis of CMML per WHO criteria \[2017\] with confirmed refractory or released disease after treatment with available therapies known to be active for CMML.

You may not qualify if:

• Has active central nervous system (CNS) leukemia.
• Has isolated extramedullary disease, i.e., no leukemic involvement in bone marrow or peripheral blood.
• Has diagnosis of acute promyelocytic leukemia or participants with known Philadelphia chromosome positive (Ph+) AML.
• Has received previous allogeneic stem cell transplant or organ transplant within 60 days of the start of study treatment.
• Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 1 year.
• Has a history of any of the following cardiovascular conditions within 6 months of screening: myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack, coronary artery bypass graft, or pulmonary embolism; has New York Heart Association (NYHA) Class III or IV congestive heart failure.
• Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody (mAB) and or any components of the study intervention, MK-0482.
• Has an active uncontrolled infection requiring directed therapy.
• Has immediately life-threatening, severe complications of leukemia such as uncontrolled bleeding, pneumonia with hypoxia or shock, or disseminated intravascular coagulation.
• Has known human immunodeficiency virus (HIV) and/or hepatitis B or C infections, or is known to be positive for HBsAg/ Hepatitis B virus (HBV) Deoxyribonucleic acid (DNA) or hepatitis C antibody or Ribonucleic acid (RNA).
• Has known psychiatric or substance abuse disorders (verbally reported) that would interfere with the participant's ability to cooperate with the requirements of the study.
• Is pregnant or breast feeding or expecting to conceive or father children within the projected duration of the study, starting with the Screening Visit through 120 days after the last dose of study intervention.
• Has received systemic anticancer therapy, radiotherapy, or surgery within 2 weeks before the start of study treatment.
• Has received hematopoietic cytokines (Granulocyte Colony Stimulating Factor (G-CSF), Granulocyte Macrophage (GM)-CSF, or erythropoietin) within 2 weeks prior to start of study treatment.
• Has received a live or live attenuated vaccine within 30 days before the first dose of study medication.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (5)

Roswell Park Cancer Institute ( Site 0006)

Buffalo, New York, 14263, United States

Location

University of Texas MD Anderson Cancer Center ( Site 0004)

Houston, Texas, 77030, United States

Location

Hadassah Medical Center ( Site 0100)

Jerusalem, 9112001, Israel

Location

Sheba Medical Center-Hemato Oncology ( Site 0101)

Ramat Gan, 5262100, Israel

Location

Hospital Universitario de Salamanca - Complejo Asistencial U-Servicio de Hematologia ( Site 0301)

Salamanca, 37007, Spain

Location

Related Links

• Merck Clinical Trials Information
• Plain Language Summary

MeSH Terms

Conditions

Recurrence; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme LLC

ClinicalTrialsDisclosure@msd.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2021
• First Posted: September 9, 2021
• Study Start: September 26, 2021
• Primary Completion: December 11, 2023
• Study Completion: December 11, 2023
• Last Updated: May 21, 2025
• Results First Posted: December 11, 2024

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

US (2); IL (2); ES (1)