Back to resultsA Clinical Study of Nemtabrutinib in Japanese Participants With Hematological Malignancies (MK-1026-002)
Primary Purpose
Mature B-cell Neoplasms
Status
Recruiting
Phase
Phase 1
Locations
Japan
Study Type
Interventional
Intervention
Nemtabrutinib
Sponsored by
About this trial
This is an interventional treatment trial for Mature B-cell Neoplasms
Eligibility Criteria
The main inclusion and exclusion criteria include but are not limited to the following: Inclusion Criteria: Histologically confirmed B-cell malignancy: Chronic lymphocytic leukemia (CLL) Small lymphocytic lymphoma (SLL) Waldenström's macroglobulinemia (WM), Lymphoplasmacytic lymphoma (LPL) Other B-cell neoplasm Failed or intolerant to either at least 2 prior regimens given in combination or sequentially OR have received 1 prior Bruton's tyrosine kinase (BTK)-containing regimen when a BTK inhibitor is approved as first line therapy Have the ability to swallow and retain oral medication Is Japanese Exclusion Criteria: Active Hepatitis B virus (HBV)/Hepatitis C virus (HCV) infection at study entry History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years Known history of human immunodeficiency virus (HIV) infection Clinically significant gastrointestinal abnormalities that might alter absorption (eg, gastric bypass surgery, gastrectomy) Underlying history of severe bleeding disorders History or concurrent condition of pneumonitis/interstitial lung disease
Sites / Locations
- Nagoya University Hospital ( Site 0003)Recruiting
- National Cancer Center Hospital East ( Site 0002)Recruiting
- Kindai University Hospital ( Site 0006)Recruiting
- Chiba Cancer Center ( Site 0005)Recruiting
- Kyushu University Hospital ( Site 0008)Recruiting
- Okayama University Hospital ( Site 0007)Recruiting
- Yamagata University Hospital ( Site 0001)Recruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Nemtabrutinib
Arm Description
Participants receive nemtabrutinib at specified dose orally once daily (QD) until progressive disease (PD) or discontinuation
Outcomes
Primary Outcome Measures
Number of Participants who Experience Dose Limiting Toxicities (DLTs) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
A DLT consists of one or more of the following toxicities: Grade ≥3 nonhematologic toxicity with exception of Grade 3 nausea, vomiting, diarrhea, rash, fatigue, and uncontrolled hypertension; Grade 4 hematologic toxicity lasting >7 days, Grade 4 platelet count decreased of any duration (with exceptions), or Grade 3 platelet count decreased with bleeding, or Grade 3 or higher febrile neutropenia of any duration; Grade 3 or Grade 4 nonhematologic laboratory abnormality, if values result in drug induced liver injury (DILI), or medical intervention is required, or the abnormality leads to hospitalization, or the abnormality persists for >1 week (with exceptions); missing >25% of nemtabrutinib doses as a result of drug-related AE(s); Grade 5 toxicity. Toxicities will be graded using NCI-CTCAE version 5.0 except hematologic toxicities in participants with chronic lymphocytic leukemia (CLL) assessed according to the International Workshop on CLL (iwCLL) criteria.
Number of Participants who Experience Adverse Events (AEs)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Number of Participants Discontinuing Study Treatment due to AEs
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Secondary Outcome Measures
Area under the Curve (AUC) of Nemtabrutinib
AUC is the area under the curve of plasma concentration of nemtabrutinib. Blood samples collected at designated timepoints will be used to determine AUC.
Maximum Concentration (Cmax) of Nemtabrutinib
Cmax is the maximum concentration of nemtabrutinib observed in plasma. Blood samples collected at designated timepoints will be used to determine Cmax.
Time to Maximum Concentration (Tmax) of Nemtabrutinib
Tmax is the time to reach maximum concentration of nemtabrutinib. Blood samples collected at designated timepoints will be used to determine Tmax.
Minimum Concentration (Cmin) of Nemtabrutinib
Cmin is the minimum concentration of nemtabrutinib observed in plasma. Blood samples collected at designated timepoints will be used to determine Cmin.
Objective Response Rate (ORR) as Assessed by Investigator
ORR is the proportion of participants in the analysis population with objective response. Objective response is defined as participants who achieve at least a partial response (PR) per disease-specific criteria as assessed by investigator.
Duration of Response (DOR) as Assessed by Investigator
For participants who demonstrate an objective response as assessed by investigator, per disease-specific criteria, duration of response is defined as the time from the first documented evidence of an objective response until disease progression or death due to any cause, whichever occurs first.
Full Information
NCT ID
NCT05673460
First Posted
January 4, 2023
Last Updated
August 23, 2023
Sponsor
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT05673460
Brief Title
A Clinical Study of Nemtabrutinib in Japanese Participants With Hematological Malignancies (MK-1026-002)
Official Title
A Phase 1 Clinical Study of Nemtabrutinib (MK-1026) in Japanese Participants With Hematological Malignancies (BELLWAVE-002)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 13, 2023 (Actual)
Primary Completion Date
March 30, 2026 (Anticipated)
Study Completion Date
March 30, 2026 (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
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of nemtabrutinib in Japanese participants with mature B-cell neoplasms.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Mature B-cell Neoplasms
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Nemtabrutinib
Arm Type
Experimental
Arm Description
Participants receive nemtabrutinib at specified dose orally once daily (QD) until progressive disease (PD) or discontinuation
Intervention Type
Drug
Intervention Name(s)
Nemtabrutinib
Other Intervention Name(s)
MK-1026, ARQ 531
Intervention Description
Nemtabrutinib tablets will be administered orally QD at dosage of 45 mg or 65 mg
Primary Outcome Measure Information:
Title
Number of Participants who Experience Dose Limiting Toxicities (DLTs) per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0
Description
A DLT consists of one or more of the following toxicities: Grade ≥3 nonhematologic toxicity with exception of Grade 3 nausea, vomiting, diarrhea, rash, fatigue, and uncontrolled hypertension; Grade 4 hematologic toxicity lasting >7 days, Grade 4 platelet count decreased of any duration (with exceptions), or Grade 3 platelet count decreased with bleeding, or Grade 3 or higher febrile neutropenia of any duration; Grade 3 or Grade 4 nonhematologic laboratory abnormality, if values result in drug induced liver injury (DILI), or medical intervention is required, or the abnormality leads to hospitalization, or the abnormality persists for >1 week (with exceptions); missing >25% of nemtabrutinib doses as a result of drug-related AE(s); Grade 5 toxicity. Toxicities will be graded using NCI-CTCAE version 5.0 except hematologic toxicities in participants with chronic lymphocytic leukemia (CLL) assessed according to the International Workshop on CLL (iwCLL) criteria.
Time Frame
Up to approximately 4 weeks
Title
Number of Participants who Experience Adverse Events (AEs)
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time Frame
Up to approximately 38 months
Title
Number of Participants Discontinuing Study Treatment due to AEs
Description
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.
Time Frame
Up to approximately 38 months
Secondary Outcome Measure Information:
Title
Area under the Curve (AUC) of Nemtabrutinib
Description
AUC is the area under the curve of plasma concentration of nemtabrutinib. Blood samples collected at designated timepoints will be used to determine AUC.
Time Frame
Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, 10, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 and 4 hours post-dose (up to ~57 days). Each cycle is 28 days
Title
Maximum Concentration (Cmax) of Nemtabrutinib
Description
Cmax is the maximum concentration of nemtabrutinib observed in plasma. Blood samples collected at designated timepoints will be used to determine Cmax.
Time Frame
Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, 10, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 and 4 hours post-dose (up to ~57 days). Each cycle is 28 days
Title
Time to Maximum Concentration (Tmax) of Nemtabrutinib
Description
Tmax is the time to reach maximum concentration of nemtabrutinib. Blood samples collected at designated timepoints will be used to determine Tmax.
Time Frame
Day 1 of Cycles 1 and 2: Pre-dose,1, 2, 4, 6, 8, 10, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 and 4 hours post-dose (up to ~57 days). Each cycle is 28 days
Title
Minimum Concentration (Cmin) of Nemtabrutinib
Description
Cmin is the minimum concentration of nemtabrutinib observed in plasma. Blood samples collected at designated timepoints will be used to determine Cmin.
Time Frame
Day 1 of Cycles 1 and 2: Pre-dose, 1, 2, 4, 6, 8, 10, and 24 hours post-dose; Day 1 of Cycle 3: pre-dose and 2 and 4 hours post-dose (up to ~57 days). Each cycle is 28 days
Title
Objective Response Rate (ORR) as Assessed by Investigator
Description
ORR is the proportion of participants in the analysis population with objective response. Objective response is defined as participants who achieve at least a partial response (PR) per disease-specific criteria as assessed by investigator.
Time Frame
Up to approximately 38 months
Title
Duration of Response (DOR) as Assessed by Investigator
Description
For participants who demonstrate an objective response as assessed by investigator, per disease-specific criteria, duration of response is defined as the time from the first documented evidence of an objective response until disease progression or death due to any cause, whichever occurs first.
Time Frame
Up to approximately 38 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
The main inclusion and exclusion criteria include but are not limited to the following:
Inclusion Criteria:
Histologically confirmed B-cell malignancy:
Chronic lymphocytic leukemia (CLL)
Small lymphocytic lymphoma (SLL)
Waldenström's macroglobulinemia (WM),
Lymphoplasmacytic lymphoma (LPL)
Other B-cell neoplasm
Failed or intolerant to either at least 2 prior regimens given in combination or sequentially OR have received 1 prior Bruton's tyrosine kinase (BTK)-containing regimen when a BTK inhibitor is approved as first line therapy
Have the ability to swallow and retain oral medication
Is Japanese
Exclusion Criteria:
Active Hepatitis B virus (HBV)/Hepatitis C virus (HCV) infection at study entry
History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 3 years
Known history of human immunodeficiency virus (HIV) infection
Clinically significant gastrointestinal abnormalities that might alter absorption (eg, gastric bypass surgery, gastrectomy)
Underlying history of severe bleeding disorders
History or concurrent condition of pneumonitis/interstitial lung disease
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Toll Free Number
Phone
1-888-577-8839
Email
Trialsites@merck.com
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
Nagoya University Hospital ( Site 0003)
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466-8560
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+81-52-741-2111
Facility Name
National Cancer Center Hospital East ( Site 0002)
City
Kashiwa
State/Province
Chiba
ZIP/Postal Code
2778577
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+81-4-7133-1111
Facility Name
Kindai University Hospital ( Site 0006)
City
Osakasayama
State/Province
Osaka
ZIP/Postal Code
589-8511
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+81-72-366-0221
Facility Name
Chiba Cancer Center ( Site 0005)
City
Chiba
ZIP/Postal Code
260-8717
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+81-43-264-5431
Facility Name
Kyushu University Hospital ( Site 0008)
City
Fukuoka
ZIP/Postal Code
812-8582
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+81-92-641-1151
Facility Name
Okayama University Hospital ( Site 0007)
City
Okayama
ZIP/Postal Code
700-8558
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+81-86-223-7151
Facility Name
Yamagata University Hospital ( Site 0001)
City
Yamagata
ZIP/Postal Code
990-9585
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Study Coordinator
Phone
+81-23-633-1122
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
Learn more about this trial
A Clinical Study of Nemtabrutinib in Japanese Participants With Hematological Malignancies (MK-1026-002)
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