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Relapsed or Refractory Acute Myeloid LeukemiaPhase 1NCT05038800

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

A Phase 1 study testing MK-0482 in people with Relapsed or Refractory Acute Myeloid Leukemia and Relapsed or Refractory Chronic Myelomonocytic Leukemia, run by Merck Sharp & Dohme LLC at 5 sites in 3 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
MK-0482
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
13 participants
Where
5 sitesin 3 countries
Study dates
26 Sep 2021to 11 Dec 2023
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • -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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

5 sites in 3 countries.

5 sites in 3 countries

United States2 sites

  • Roswell Park Cancer Institute ( Site 0006)

    Buffalo, New York, 14263

  • University of Texas MD Anderson Cancer Center ( Site 0004)

    Houston, Texas, 77030

Other trials in United States

Israel2 sites

  • Hadassah Medical Center ( Site 0100)

    Jerusalem, 9112001

  • Sheba Medical Center-Hemato Oncology ( Site 0101)

    Ramat Gan, 5262100

Other trials in Israel

Spain1 site

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

    Salamanca, 37007

Other trials in Spain

About this study

Official title: A Phase 1b Study to Evaluate the Safety, Tolerability, and Pharmacokinetics/Pharmacodynamics of MK-0482 in Participants With Relapsed or Refractory Acute Myeloid Leukemia or Chronic Myelomonocytic Leukemia

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.

Read the detailed description

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.

Being tested
MK-0482
Medical subject headings
Recurrence, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MK-0482Biological

    IV infusion

Study groups in NCT05038800
Study groupRoleWhat they receive
MK-0482 7.5 mg Q3WExperimentalParticipants 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).
Receives: Biological: MK-0482
MK-0482 25 mg Q3WExperimentalParticipants 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).
Receives: Biological: MK-0482
MK-0482 75 mg Q3WExperimentalParticipants 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).
Receives: Biological: MK-0482
MK-0482 225 mg Q3WExperimentalParticipants 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).
Receives: Biological: MK-0482
MK-0482 750 mg Q3WExperimentalParticipants 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).
Receives: Biological: MK-0482

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Cycle 1 (up to 21 days)

  2. 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.

    Measured: Up to approximately 10 months

  3. 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.

    Measured: Up to approximately 4 months

Secondary outcomes (8)

  1. Maximum Concentration (Cmax) of MK-0482

    Cmax was defined as the maximum concentration of MK-0482 observed in plasma. Blood samples were collected pre-dose and post-dose at designated timepoints to determine Cmax of MK-0482.

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

  2. Minimum Concentration (Cmin) of MK-0482

    Cmin (or Ctrough) was defined as the lowest concentration of MK-0482 reached during a dosing interval (time interval between administration of two doses). Blood samples were collected pre-dose and post-dose at designated timepoints to determine Cmin of MK-0482.

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

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

    AUC0-21 was defined as the area under the plasma concentration-time curve from time zero to 21 days. Blood samples were collected pre-dose and post-dose at designated timepoints to determine AUC0-21 of MK-0482.

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

  4. Time to Maximum Concentration (Tmax) of MK-0482

    Tmax was defined as the time to maximum concentration of MK-0482 observed in plasma. Blood samples were collected pre-dose and post-dose at designated timepoints to determine Tmax of MK-0482.

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

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

    t½ was defined as the time required to divide the MK-0482 plasma concentration by two after reaching pseudo-equilibrium. Blood samples were collected pre-dose and post-dose at designated timepoints to determine t½ of MK-0482.

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

  6. Complete Remission (CR) Rate

    CR Rate was assessed by the investigator per 2017 European Leukemia Net (ELN) Response Criteria for Acute Myeloid Leukemia (AML) and was defined as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count (ANC) ≥1.0 × 10^9/L (1000/µL); and platelet count ≥100 × 10^9/L (100,000/µL). The percentage of participants with CR (CR Rate) was reported for each arm.

    Measured: Up to approximately 10 months

  7. Composite CR Rate

    Composite CR rate was assessed by the investigator per 2017 ELN Response Criteria for AML and was defined as CR plus CR with incomplete recovery (CRi). CR was defined as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 10^9/L (1000/µL); and platelet count ≥100 × 10^9/L (100,000/µL). CRi was defined as all CR criteria except for residual neutropenia (<1.0 × 10^9/L [1000/µL]) or thrombocytopenia (<100 × 10^9/L [100,000/µL]). The percentage of participants with Composite CR (Composite CR Rate) was reported for each arm.

    Measured: Up to approximately 10 months

  8. Objective Response Rate (ORR)

    ORR was assessed by the investigator per 2017 ELN Response Criteria for AML and was defined as the combined percentage of participants with CR, CRi, and partial remission (PR). CR was defined as bone marrow blasts <5%; absence of circulating blasts and blasts with Auer rods; absence of extramedullary disease; ANC ≥1.0 × 10^9/L (1000/µL); platelet count ≥100 × 10^9/L (100,000/µL)]. CRi was defined as all CR criteria except for residual neutropenia (<1.0 × 10^9/L [1000/µL]) or thrombocytopenia (<100 × 10^9/L [100,000/µL]). PR was defined as all hematologic criteria of CR; decrease of bone marrow blast percentage to 5% to 25%; and decrease of pre-treatment bone marrow blast percentage by at least 50%). ORR was reported for each arm.

    Measured: Up to approximately 10 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Sep 2021
  2. Study start26 Sep 2021
  3. Primary completion11 Dec 2023
  4. Study completion11 Dec 2023

Why it stopped: Business Reasons

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
13 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05038800
Sponsor's protocol ID
0482-002
Other IDs
MK-0482-002, 2023-003740-27-00, U1111-1287-5269, 2022-003740-27, 2023
Status last verified
May 2025
First submitted
24 Aug 2021
Last updated
21 May 2025
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing MK-0482 in people with Relapsed or Refractory Acute Myeloid Leukemia and Relapsed or Refractory Chronic Myelomonocytic Leukemia, run by Merck Sharp & Dohme LLC at 5 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 1 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 21 May 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in United States, Israel, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Dec 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants Who Experienced a Dose-Limiting Toxicity (DLT) (time frame: Cycle 1 (up to 21 days)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05038800.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2025.

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