Back to resultsLong-term Safety and Efficacy of Momelotinib in Subjects With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, Polycythemia Vera or Essential Thrombocythemia
Primary Purpose
Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Momelotinib
Sponsored by
About this trial
This is an interventional treatment trial for Primary Myelofibrosis focused on measuring Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, Post Essential Thrombocythemia Myelofibrosis, Polycythemia Vera, Essential Thrombocythemia, blood disorders
Eligibility Criteria
Key Inclusion Criteria:
- Currently enrolled in study CCL09101E, or YM387-II-02, or successfully completed 24 weeks of study GS-US-352-1672
- Able to comprehend and willing to sign informed consent form
Key Exclusion Criteria:
- Known hypersensitivity to momelotinib, its metabolites, or formulation excipients
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Cohort 1
Cohort 2
Cohort 3
Cohort 4
Arm Description
Participants previously enrolled in Study CCL09191E will receive momelotinib for approximately 4 years.
Participants previously enrolled in Study YM387-II-02 will receive momelotinib for approximately 4 years.
Participants previously enrolled in Study GS-US-354-0101 will receive momelotinib for up to 4 years. Cohort 3 was closed and all enrolled participants were discontinued from this study because parent Study GS-US-354-0101 was terminated.
Participants previously enrolled in Study GS-US-352-1672 will receive momelotinib for approximately 4 years.
Outcomes
Primary Outcome Measures
Long Term Safety and Tolerability as Measured by the Incidence and Severity of Adverse Events and Clinical Laboratory Abnormalities
Long-term safety and tolerability profile of momelotinib based on safety data (adverse events and selected hematology and chemistry laboratory parameters) collected after the first dose of momelotinib in the parent study.
Secondary Outcome Measures
Splenic Response Rate
The number of subjects achieving a spleen response, defined as a reduction of 50% or more in palpable splenomegaly of a spleen that was at least 10 cm below the LCM at baseline, or a spleen that was palpable at > 5 cm and < 10 cm below the LCM at baseline becoming not palpable for at least 56 days, using baseline of the parent study as the reference.
Duration of Splenic Response
The interval from the first onset of splenic response (in the parent study or Study GS-US-352-1154) to the earliest date of loss of splenic response. Loss of response was defined as the reduction of splenomegaly by < 50% among responders (with splenomegaly ≥ 10 cm below the LCM at baseline) that lasts ≥ 56 days, or the recurrence of > 0 cm splenomegaly among responders (with splenomegaly > 5 and < 10 cm at baseline) that lasts ≥ 56 days.
Duration of splenic response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.
Transfusion Independence Response Rate
The number of transfusion dependent subjects at entry to a parent study who became transfusion-independent for ≥ 12 weeks at any time from the first dose of momelotinib in the parent study until the end of Study GS-US-352-1154.
Duration of Transfusion Independence Response
The interval from the first onset date of transfusion independence (in the parent study or Study GS-US-352-1154) to the earliest date of loss of response for participants who are transfusion dependent at baseline in the parent study. Loss of TI response was defined as receiving an RBC transfusion after achieving a TI response.
Duration of transfusion independence response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.
Anemia Response Rate
The number of subjects achieving an anemia response, defined as:
Achieving transfusion independence for ≥ 12 weeks, for subjects who were transfusion-dependent at baseline in the parent study, or
Having ≥ 2 g/dL increase in Hgb from baseline for ≥ 12 weeks, for subjects with Hgb < 10 g/dL at baseline in the parent study who were not transfusion-dependent (Cohort 1) or who were transfusion-independent (Cohort 2).
Duration of Anemia Response
The interval from the first onset of anemia response (in the parent study or Study GS-US-352-1154) to the earliest date of loss of anemia response. Loss of anemia response was defined as having any RBC transfusion after achieving an anemia response.
Duration of anemia response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.
Rate of RBC Transfusion
The average number of RBC units per subject month during the parent study and/or Study GS-US-352-1154.
Overall Survival
The interval from the first dose of momelotinib in the parent study until death from any cause.
Overall survival was analyzed using the Kaplan-Meier method. Data from subjects who were lost to follow-up or remained alive until the end of the study were censored at the date of last contact or last response assessment.
Progression-Free Survival
The interval from the first dose of momelotinib in the parent study until the first documentation of definitive progressive disease as defined in 2006 IWG-MRT or death due to any cause.
Subjects who were free of progression were censored at the last assessment date.
Leukemia-Free Survival
The interval from the first dose of momelotinib in the parent study until the first documented leukemic transformation or death from any cause. Leukemic transformation was documented in the adverse event electronic case report form.
Leukemia-free survival was analyzed using the Kaplan-Meier method. Subjects who were free of leukemia transformation were censored at the last assessment date.
Full Information
NCT ID
NCT02124746
First Posted
April 24, 2014
Last Updated
June 14, 2023
Sponsor
Sierra Oncology LLC - a GSK company
1. Study Identification
Unique Protocol Identification Number
NCT02124746
Brief Title
Long-term Safety and Efficacy of Momelotinib in Subjects With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, Polycythemia Vera or Essential Thrombocythemia
Official Title
Open-label Study to Assess the Long-term Safety and Efficacy of Momelotinib in Subjects With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post Essential Thrombocythemia Myelofibrosis, Polycythemia Vera or Essential Thrombocythemia
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
April 30, 2014 (Actual)
Primary Completion Date
December 6, 2018 (Actual)
Study Completion Date
December 6, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sierra Oncology LLC - a GSK company
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
This open-label study is to determine the long-term safety and tolerability of momelotinib in previously enrolled study participants with primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), post-essential thrombocythemia myelofibrosis (post-ET MF), polycythemia vera (PV), or essential thrombocythemia (ET), who have tolerated and achieved stable disease or better with momelotinib treatment while enrolled in a previous clinical trial.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis, Polycythemia Vera, Essential Thrombocythemia
Keywords
Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, Post Essential Thrombocythemia Myelofibrosis, Polycythemia Vera, Essential Thrombocythemia, blood disorders
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
87 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Cohort 1
Arm Type
Experimental
Arm Description
Participants previously enrolled in Study CCL09191E will receive momelotinib for approximately 4 years.
Arm Title
Cohort 2
Arm Type
Experimental
Arm Description
Participants previously enrolled in Study YM387-II-02 will receive momelotinib for approximately 4 years.
Arm Title
Cohort 3
Arm Type
Experimental
Arm Description
Participants previously enrolled in Study GS-US-354-0101 will receive momelotinib for up to 4 years.
Cohort 3 was closed and all enrolled participants were discontinued from this study because parent Study GS-US-354-0101 was terminated.
Arm Title
Cohort 4
Arm Type
Experimental
Arm Description
Participants previously enrolled in Study GS-US-352-1672 will receive momelotinib for approximately 4 years.
Intervention Type
Drug
Intervention Name(s)
Momelotinib
Other Intervention Name(s)
GS-0387, CYT387
Intervention Description
Momelotinib tablets administered orally once daily
Primary Outcome Measure Information:
Title
Long Term Safety and Tolerability as Measured by the Incidence and Severity of Adverse Events and Clinical Laboratory Abnormalities
Description
Long-term safety and tolerability profile of momelotinib based on safety data (adverse events and selected hematology and chemistry laboratory parameters) collected after the first dose of momelotinib in the parent study.
Time Frame
From the first dose of momelotinib in the parent study to 30 days following permanent discontinuation of momelotinib in Study GS-US-352-1154.
Secondary Outcome Measure Information:
Title
Splenic Response Rate
Description
The number of subjects achieving a spleen response, defined as a reduction of 50% or more in palpable splenomegaly of a spleen that was at least 10 cm below the LCM at baseline, or a spleen that was palpable at > 5 cm and < 10 cm below the LCM at baseline becoming not palpable for at least 56 days, using baseline of the parent study as the reference.
Time Frame
From baseline in the parent study until the last spleen assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.
Title
Duration of Splenic Response
Description
The interval from the first onset of splenic response (in the parent study or Study GS-US-352-1154) to the earliest date of loss of splenic response. Loss of response was defined as the reduction of splenomegaly by < 50% among responders (with splenomegaly ≥ 10 cm below the LCM at baseline) that lasts ≥ 56 days, or the recurrence of > 0 cm splenomegaly among responders (with splenomegaly > 5 and < 10 cm at baseline) that lasts ≥ 56 days.
Duration of splenic response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.
Time Frame
From baseline in the parent study until the last spleen assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.
Title
Transfusion Independence Response Rate
Description
The number of transfusion dependent subjects at entry to a parent study who became transfusion-independent for ≥ 12 weeks at any time from the first dose of momelotinib in the parent study until the end of Study GS-US-352-1154.
Time Frame
From baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.
Title
Duration of Transfusion Independence Response
Description
The interval from the first onset date of transfusion independence (in the parent study or Study GS-US-352-1154) to the earliest date of loss of response for participants who are transfusion dependent at baseline in the parent study. Loss of TI response was defined as receiving an RBC transfusion after achieving a TI response.
Duration of transfusion independence response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.
Time Frame
From baseline in the parent study until the last assessment date in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.
Title
Anemia Response Rate
Description
The number of subjects achieving an anemia response, defined as:
Achieving transfusion independence for ≥ 12 weeks, for subjects who were transfusion-dependent at baseline in the parent study, or
Having ≥ 2 g/dL increase in Hgb from baseline for ≥ 12 weeks, for subjects with Hgb < 10 g/dL at baseline in the parent study who were not transfusion-dependent (Cohort 1) or who were transfusion-independent (Cohort 2).
Time Frame
From baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.
Title
Duration of Anemia Response
Description
The interval from the first onset of anemia response (in the parent study or Study GS-US-352-1154) to the earliest date of loss of anemia response. Loss of anemia response was defined as having any RBC transfusion after achieving an anemia response.
Duration of anemia response was measured by descriptive statistics. Data from responders who maintained their response was censored at the last assessment date.
Time Frame
From baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.
Title
Rate of RBC Transfusion
Description
The average number of RBC units per subject month during the parent study and/or Study GS-US-352-1154.
Time Frame
From the first dose of momelotinib in the parent study until the last dose of momelotinib in Study GS-US-352-1154.
Title
Overall Survival
Description
The interval from the first dose of momelotinib in the parent study until death from any cause.
Overall survival was analyzed using the Kaplan-Meier method. Data from subjects who were lost to follow-up or remained alive until the end of the study were censored at the date of last contact or last response assessment.
Time Frame
From baseline in the parent study until the date of last contact or last response assessment, up to 30 days following permanent discontinuation of momelotinib.
Title
Progression-Free Survival
Description
The interval from the first dose of momelotinib in the parent study until the first documentation of definitive progressive disease as defined in 2006 IWG-MRT or death due to any cause.
Subjects who were free of progression were censored at the last assessment date.
Time Frame
From baseline in the parent study until the last response assessment, up to 30 days following permanent discontinuation of momelotinib.
Title
Leukemia-Free Survival
Description
The interval from the first dose of momelotinib in the parent study until the first documented leukemic transformation or death from any cause. Leukemic transformation was documented in the adverse event electronic case report form.
Leukemia-free survival was analyzed using the Kaplan-Meier method. Subjects who were free of leukemia transformation were censored at the last assessment date.
Time Frame
From baseline in the parent study until the date of the last assessment, up to 30 days following permanent discontinuation of momelotinib.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Currently enrolled in study CCL09101E, or YM387-II-02, or successfully completed 24 weeks of study GS-US-352-1672
Able to comprehend and willing to sign informed consent form
Key Exclusion Criteria:
Known hypersensitivity to momelotinib, its metabolites, or formulation excipients
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
City
Scottsdale
State/Province
Arizona
Country
United States
City
Orange
State/Province
California
Country
United States
City
Stanford
State/Province
California
Country
United States
City
Whittier
State/Province
California
Country
United States
City
Jacksonville
State/Province
Florida
Country
United States
City
Baltimore
State/Province
Maryland
Country
United States
City
Boston
State/Province
Massachusetts
Country
United States
City
Ann Arbor
State/Province
Michigan
Country
United States
City
Rochester
State/Province
Minnesota
Country
United States
City
Saint Louis
State/Province
Missouri
Country
United States
City
Bronx
State/Province
New York
Country
United States
City
New York
State/Province
New York
Country
United States
City
Cleveland
State/Province
Ohio
Country
United States
City
Houston
State/Province
Texas
Country
United States
City
Salt Lake City
State/Province
Utah
Country
United States
City
Frankston
State/Province
Victoria
Country
Australia
City
Parkville
State/Province
Victoria
Country
Australia
City
Toronto
State/Province
Ontario
Country
Canada
City
Montreal
State/Province
Quebec
Country
Canada
City
La Tronche
Country
France
City
Paris
Country
France
City
Minden
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Long-term Safety and Efficacy of Momelotinib in Subjects With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis, Polycythemia Vera or Essential Thrombocythemia
We'll reach out to this number within 24 hrs