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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

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ClinicalTrials.gov Identifier: NCT02124746
Recruitment Status : Completed
First Posted : April 28, 2014
Results First Posted : February 5, 2021
Last Update Posted : February 5, 2021
Sponsor:
Information provided by (Responsible Party):
Sierra Oncology, Inc.

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.

Condition or disease Intervention/treatment Phase
Primary Myelofibrosis Post-Polycythemia Vera Myelofibrosis Post-Essential Thrombocythemia Myelofibrosis Polycythemia Vera Essential Thrombocythemia Drug: Momelotinib Phase 2

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 87 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : April 30, 2014
Actual Primary Completion Date : December 6, 2018
Actual Study Completion Date : December 6, 2018


Arm Intervention/treatment
Experimental: Cohort 1
Participants previously enrolled in Study CCL09191E will receive momelotinib for approximately 4 years.
Drug: Momelotinib
Momelotinib tablets administered orally once daily
Other Names:
  • GS-0387
  • CYT387

Experimental: Cohort 2
Participants previously enrolled in Study YM387-II-02 will receive momelotinib for approximately 4 years.
Drug: Momelotinib
Momelotinib tablets administered orally once daily
Other Names:
  • GS-0387
  • CYT387

Experimental: Cohort 3

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.

Drug: Momelotinib
Momelotinib tablets administered orally once daily
Other Names:
  • GS-0387
  • CYT387

Experimental: Cohort 4
Participants previously enrolled in Study GS-US-352-1672 will receive momelotinib for approximately 4 years.
Drug: Momelotinib
Momelotinib tablets administered orally once daily
Other Names:
  • GS-0387
  • CYT387




Primary Outcome Measures :
  1. Long Term Safety and Tolerability as Measured by the Incidence and Severity of Adverse Events and Clinical Laboratory Abnormalities [ 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. ]
    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 :
  1. Splenic Response Rate [ 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. ]
    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.

  2. Duration of Splenic Response [ 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. ]

    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.


  3. Transfusion Independence Response Rate [ 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. ]
    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.

  4. Duration of Transfusion Independence Response [ 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. ]

    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.


  5. Anemia Response Rate [ 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. ]

    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).

  6. Duration of Anemia Response [ 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. ]

    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.


  7. Rate of RBC Transfusion [ Time Frame: From the first dose of momelotinib in the parent study until the last dose of momelotinib in Study GS-US-352-1154. ]
    The average number of RBC units per subject month during the parent study and/or Study GS-US-352-1154.

  8. Overall Survival [ 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. ]

    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.


  9. Progression-Free Survival [ Time Frame: From baseline in the parent study until the last response assessment, up to 30 days following permanent discontinuation of momelotinib. ]

    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.


  10. Leukemia-Free Survival [ Time Frame: From baseline in the parent study until the date of the last assessment, up to 30 days following permanent discontinuation of momelotinib. ]

    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.




Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02124746


Locations
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United States, Arizona
Scottsdale, Arizona, United States
United States, California
Orange, California, United States
Stanford, California, United States
Whittier, California, United States
United States, Florida
Jacksonville, Florida, United States
United States, Maryland
Baltimore, Maryland, United States
United States, Massachusetts
Boston, Massachusetts, United States
United States, Michigan
Ann Arbor, Michigan, United States
United States, Minnesota
Rochester, Minnesota, United States
United States, Missouri
Saint Louis, Missouri, United States
United States, New York
Bronx, New York, United States
New York, New York, United States
United States, Ohio
Cleveland, Ohio, United States
United States, Texas
Houston, Texas, United States
United States, Utah
Salt Lake City, Utah, United States
Australia, Victoria
Frankston, Victoria, Australia
Parkville, Victoria, Australia
Canada, Ontario
Toronto, Ontario, Canada
Canada, Quebec
Montreal, Quebec, Canada
France
La Tronche, France
Paris, France
Germany
Minden, Germany
Sponsors and Collaborators
Sierra Oncology, Inc.
Investigators
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Study Director: Gilead Study Director Gilead Sciences
  Study Documents (Full-Text)

Documents provided by Sierra Oncology, Inc.:
Study Protocol  [PDF] November 6, 2017
Statistical Analysis Plan  [PDF] April 26, 2019

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Responsible Party: Sierra Oncology, Inc.
ClinicalTrials.gov Identifier: NCT02124746    
Other Study ID Numbers: GS-US-352-1154
2013-004476-36 ( EudraCT Number )
First Posted: April 28, 2014    Key Record Dates
Results First Posted: February 5, 2021
Last Update Posted: February 5, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Sierra Oncology, Inc.:
Primary Myelofibrosis
Post Polycythemia Vera Myelofibrosis
Post Essential Thrombocythemia Myelofibrosis
Polycythemia Vera
Essential Thrombocythemia
blood disorders
Additional relevant MeSH terms:
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Polycythemia Vera
Primary Myelofibrosis
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders
N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action