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

Phase 2

Completed

Conditions: Polycythemia Vera
Essential Thrombocythemia
Post-Polycythemia Vera Myelofibrosis
Primary Myelofibrosis
Post-Essential Thrombocythemia Myelofibrosis

Interventions: Drug: Momelotinib

Registration Number: NCT02124746

Lead Sponsor: Sierra Oncology LLC - a GSK company

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 87

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 2	Momelotinib	Participants previously enrolled in Study YM387-II-02 will receive momelotinib for approximately 4 years.
Cohort 3	Momelotinib	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.
Cohort 1	Momelotinib	Participants previously enrolled in Study CCL09191E will receive momelotinib for approximately 4 years.
Cohort 4	Momelotinib	Participants previously enrolled in Study GS-US-352-1672 will receive momelotinib for approximately 4 years.

Primary Outcome Measures

Name	Time	Method
Long Term Safety and Tolerability as Measured by the Incidence and Severity of Adverse Events and Clinical Laboratory Abnormalities	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

Name	Time	Method
Duration of Anemia Response	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.
Rate of RBC Transfusion	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.
Leukemia-Free Survival	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.
Duration of Splenic Response	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.
Splenic Response Rate	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.
Transfusion Independence Response Rate	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.
Duration of Transfusion Independence Response	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.
Anemia Response Rate	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).
Overall Survival	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.
Progression-Free Survival	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.