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

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Myelofibrosis; Polycythemia Vera; Essential Thrombocythemia; Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis
• Intervention / Treatment: Drug: Momelotinib

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Frankston, Victoria, Australia
    • Parkville, Victoria, Australia
• Canada
  • Ontario
    • Toronto, Ontario, Canada
  • Quebec
    • Montreal, Quebec, Canada
• France
  • La Tronche, France
  • Paris, France
• Germany
  • Minden, Germany
• United States
  • Arizona
    • Scottsdale, Arizona, United States
  • California
    • Orange, California, United States
    • Stanford, California, United States
    • Whittier, California, United States
  • Florida
    • Jacksonville, Florida, United States
  • Maryland
    • Baltimore, Maryland, United States
  • Massachusetts
    • Boston, Massachusetts, United States
  • Michigan
    • Ann Arbor, Michigan, United States
  • Minnesota
    • Rochester, Minnesota, United States
  • Missouri
    • Saint Louis, Missouri, United States
  • New York
    • Bronx, New York, United States
    • New York, New York, United States
  • Ohio
    • Cleveland, Ohio, United States
  • Texas
    • Houston, Texas, United States
  • Utah
    • Salt Lake City, Utah, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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 Measures

Outcome Measure	Measure Description	Time Frame
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.	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.
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.	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.
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.	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.
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.	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.
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).	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.
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.	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.
Rate of RBC Transfusion	The average number of RBC units per subject month during the parent study and/or Study GS-US-352-1154.	From the first dose of momelotinib in the parent study until the last dose of momelotinib in 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.	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.
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.	From baseline in the parent study until the last response assessment, up to 30 days following permanent discontinuation of momelotinib.
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.	From baseline in the parent study until the date of the last assessment, up to 30 days following permanent discontinuation of momelotinib.

Collaborators and Investigators

• Sponsor: Sierra Oncology LLC - a GSK company
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Study record dates

Study Major Dates

• Study Start (Actual): April 30, 2014
• Primary Completion (Actual): December 6, 2018
• Study Completion (Actual): December 6, 2018

Study Registration Dates

• First Submitted: April 24, 2014
• First Submitted That Met QC Criteria: April 24, 2014
• First Posted (Estimated): April 28, 2014

Study Record Updates

• Last Update Posted (Estimated): June 19, 2023
• Last Update Submitted That Met QC Criteria: June 14, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Essential Thrombocythemia; Primary Myelofibrosis; blood disorders; Polycythemia Vera; Post Polycythemia Vera Myelofibrosis; Post Essential Thrombocythemia Myelofibrosis
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Myeloproliferative Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Bone Marrow Neoplasms; Hematologic Neoplasms; Primary Myelofibrosis; Thrombocytosis; Thrombocythemia, Essential; Polycythemia Vera; Polycythemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide
• Other Study ID Numbers: GS-US-352-1154; 2013-004476-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No