Back to resultsA Study to Evaluate MK-0482 for Relapsed/Refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML) (MK-0482-002)
Primary Purpose
Relapsed or Refractory Acute Myeloid Leukemia, Relapsed or Refractory Chronic Myelomonocytic Leukemia
Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
MK-0482
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed or Refractory Acute Myeloid Leukemia
Eligibility Criteria
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.
Sites / Locations
- Roswell Park Cancer Institute ( Site 0006)
- University of Texas MD Anderson Cancer Center ( Site 0004)
- Hadassah Medical Center ( Site 0100)
- Sheba Medical Center-Hemato Oncology ( Site 0101)
- Hospital Universitario de Salamanca - Complejo Asistencial U-Servicio de Hematologia ( Site 0301)
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
MK-0482
Arm Description
Participants will receive MK-0482 monotherapy administered in escalating doses as an intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles.
Outcomes
Primary Outcome Measures
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)
DLTs are defined as any of the following assessed as treatment (Tx)-related by investigator: Grade (Gr) 4 non-hematologic toxicity (T); Gr 3 non-hematologic T; Gr 3 or Gr 4 non-hematologic T lasting >7 days; Gr 4 neutropenia or thrombocytopenia lasting >14 days; >2 week-delay in starting Cycle 2 due to Tx-related T; Tx related T resulting in Tx discontinuation during DLT evaluation period; missing >25% of the MK-0482 during DLT evaluation period resulting from Tx-related AE; or Gr5 toxicity.
Number of Participants Who Experience at Least One Adverse Event (AE)
An AE is 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 experience at least one AE will be presented.
Number of Participants Who Discontinue Study Treatment Due to an AE
An AE is 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 discontinue study treatment due to an AE will be presented.
Secondary Outcome Measures
Maximum Concentration (Cmax)
Cmax is the maximum concentration of the drug observed in plasma. Blood samples will be collected pre-dose and post-dose at designated timepoints to determine Cmax of MK-0482.
Trough Plasma Concentration (Ctrough)
Ctrough is the lowest concentration reached by a drug before the next dose is administered. Blood samples will be collected pre-dose and post-dose at designated timepoints to determine Ctrough of MK-0482.
Complete Remission (CR) Rate
CR is 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); platelet count ≥100 × 10^9/L (100,000/µL).
Composite CR Rate
Composite CR rate is defined as CR + CR with incomplete recovery (CRi). CR is 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 is 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]).
Objective Response Rate (ORR)
Objective response: CR + CRi + partial remission (PR) ORR is defined as the percentage of participants who have a complete response (CR: CR is 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); platelet count ≥100 × 10^9/L (100,000/µL)) and CR with incomplete hematologic recovery (CRi: CRi is 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]) and partial response (PR: PR is 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%).
Full Information
NCT ID
NCT05038800
First Posted
August 24, 2021
Last Updated
October 17, 2023
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT05038800
Brief Title
A Study to Evaluate MK-0482 for Relapsed/Refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML) (MK-0482-002)
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
Study Type
Interventional
2. Study Status
Record Verification Date
October 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 26, 2021 (Actual)
Primary Completion Date
August 25, 2025 (Anticipated)
Study Completion Date
August 25, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed or Refractory Acute Myeloid Leukemia, Relapsed or Refractory Chronic Myelomonocytic Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
35 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
MK-0482
Arm Type
Experimental
Arm Description
Participants will receive MK-0482 monotherapy administered in escalating doses as an intravenous (IV) infusion on Day 1 of each 21-day cycle for up to 35 cycles.
Intervention Type
Biological
Intervention Name(s)
MK-0482
Intervention Description
IV infusion
Primary Outcome Measure Information:
Title
Number of Participants Who Experience a Dose-Limiting Toxicity (DLT)
Description
DLTs are defined as any of the following assessed as treatment (Tx)-related by investigator: Grade (Gr) 4 non-hematologic toxicity (T); Gr 3 non-hematologic T; Gr 3 or Gr 4 non-hematologic T lasting >7 days; Gr 4 neutropenia or thrombocytopenia lasting >14 days; >2 week-delay in starting Cycle 2 due to Tx-related T; Tx related T resulting in Tx discontinuation during DLT evaluation period; missing >25% of the MK-0482 during DLT evaluation period resulting from Tx-related AE; or Gr5 toxicity.
Time Frame
Cycle 1 (up to 21 days)
Title
Number of Participants Who Experience at Least One Adverse Event (AE)
Description
An AE is 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 experience at least one AE will be presented.
Time Frame
Up to approximately 27 months
Title
Number of Participants Who Discontinue Study Treatment Due to an AE
Description
An AE is 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 discontinue study treatment due to an AE will be presented.
Time Frame
Up to approximately 24 months
Secondary Outcome Measure Information:
Title
Maximum Concentration (Cmax)
Description
Cmax is the maximum concentration of the drug observed in plasma. Blood samples will be collected pre-dose and post-dose at designated timepoints to determine Cmax of MK-0482.
Time Frame
Pre- and post-dose: Day 1 of Cycles 1, 2, 3, 4, 6, 8 and every 4 Cycles thereafter up to 35 Cycles (through study completion, an average of 2 years). Post-dose: Cycle 1 on Days 2, 4, 8, 15, and Cycles 2 and 3 on Day 8. Each Cycle=21 days.
Title
Trough Plasma Concentration (Ctrough)
Description
Ctrough is the lowest concentration reached by a drug before the next dose is administered. Blood samples will be collected pre-dose and post-dose at designated timepoints to determine Ctrough of MK-0482.
Time Frame
Pre- and post-dose: Day 1 of Cycles 1, 2, 3, 4, 6, 8 and every 4 Cycles thereafter up to 35 Cycles (through study completion, an average of 2 years). Post-dose: Cycle 1 on Days 2, 4, 8, 15, and Cycles 2 and 3 on Day 8. Each Cycle=21 days.
Title
Complete Remission (CR) Rate
Description
CR is 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); platelet count ≥100 × 10^9/L (100,000/µL).
Time Frame
Up to approximately 24 months
Title
Composite CR Rate
Description
Composite CR rate is defined as CR + CR with incomplete recovery (CRi). CR is 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 is 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]).
Time Frame
Up to approximately 24 months
Title
Objective Response Rate (ORR)
Description
Objective response: CR + CRi + partial remission (PR) ORR is defined as the percentage of participants who have a complete response (CR: CR is 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); platelet count ≥100 × 10^9/L (100,000/µL)) and CR with incomplete hematologic recovery (CRi: CRi is 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]) and partial response (PR: PR is 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%).
Time Frame
Up to approximately 24 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Merck Sharp & Dohme LLC
Official's Role
Study Director
Facility Information:
Facility Name
Roswell Park Cancer Institute ( Site 0006)
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
University of Texas MD Anderson Cancer Center ( Site 0004)
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Hadassah Medical Center ( Site 0100)
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Facility Name
Sheba Medical Center-Hemato Oncology ( Site 0101)
City
Ramat Gan
ZIP/Postal Code
5262100
Country
Israel
Facility Name
Hospital Universitario de Salamanca - Complejo Asistencial U-Servicio de Hematologia ( Site 0301)
City
Salamanca
ZIP/Postal Code
37007
Country
Spain
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
IPD Sharing URL
http://engagezone.msd.com/ds_documentation.php
Links:
URL
https://www.merckclinicaltrials.com/
Description
Merck Clinical Trials Information
URL
https://trialstransparency.merckclinicaltrials.com/Study.aspx?id=0482-002&kw=0482-002
Description
Plain Language Summary
Learn more about this trial
A Study to Evaluate MK-0482 for Relapsed/Refractory Acute Myeloid Leukemia (AML) or Chronic Myelomonocytic Leukemia (CMML) (MK-0482-002)
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