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

NCT ID: NCT05038800

Last Updated: 2025-05-21

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

13 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-09-26

Study Completion Date

2023-12-11

Brief Summary

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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.

Detailed Description

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In Part 1, single participants will be enrolled sequentially into escalating dose levels. Progression from one dose level to the next higher dose level will be based on the evaluation of dose-limiting toxicity (DLT). Once a preliminary RP2D is identified in Part 1, approximately 10 to 15 additional participants with R/R AML will be enrolled at the RP2D for Part 2.

Conditions

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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MK-0482 7.5 mg Q3W

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).

Group Type EXPERIMENTAL

MK-0482

Intervention Type BIOLOGICAL

IV infusion

MK-0482 25 mg Q3W

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).

Group Type EXPERIMENTAL

MK-0482

Intervention Type BIOLOGICAL

IV infusion

MK-0482 75 mg Q3W

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).

Group Type EXPERIMENTAL

MK-0482

Intervention Type BIOLOGICAL

IV infusion

MK-0482 225 mg Q3W

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).

Group Type EXPERIMENTAL

MK-0482

Intervention Type BIOLOGICAL

IV infusion

MK-0482 750 mg Q3W

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).

Group Type EXPERIMENTAL

MK-0482

Intervention Type BIOLOGICAL

IV infusion

Interventions

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MK-0482

IV infusion

Intervention Type BIOLOGICAL

Eligibility Criteria

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Inclusion Criteria

-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.

Exclusion Criteria

* 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.
* Is currently participating and receiving study intervention in a study of an investigational agent or has participated and received study intervention in a study of an investigational agent or has used an investigational device within 14 days of administration of MK-0482.
* Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Director

Role: STUDY_DIRECTOR

Merck Sharp & Dohme LLC

Locations

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Roswell Park Cancer Institute ( Site 0006)

Buffalo, New York, United States

Site Status

University of Texas MD Anderson Cancer Center ( Site 0004)

Houston, Texas, United States

Site Status

Hadassah Medical Center ( Site 0100)

Jerusalem, , Israel

Site Status

Sheba Medical Center-Hemato Oncology ( Site 0101)

Ramat Gan, , Israel

Site Status

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

Salamanca, , Spain

Site Status

Countries

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United States Israel Spain

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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MK-0482-002

Identifier Type: OTHER

Identifier Source: secondary_id

2023-003740-27-00

Identifier Type: REGISTRY

Identifier Source: secondary_id

U1111-1287-5269

Identifier Type: REGISTRY

Identifier Source: secondary_id

2022-003740-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

0482-002

Identifier Type: -

Identifier Source: org_study_id

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