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 Overview
=================
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.

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

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

Intervention / Treatment
-----------------
* Drug: Momelotinib


Participation Criteria
=================
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Participants previously enrolled in Study CCL09191E will receive momelotinib for approximately 4 years. | Drug: Momelotinib<br>* Momelotinib tablets administered orally once daily<br>* Other names: CYT387;|
| Experimental: Cohort 2<br>Participants previously enrolled in Study YM387-II-02 will receive momelotinib for approximately 4 years. | Drug: Momelotinib<br>* Momelotinib tablets administered orally once daily<br>* Other names: CYT387;|
| Experimental: Cohort 3<br>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<br>* Momelotinib tablets administered orally once daily<br>* Other names: CYT387;|
| Experimental: Cohort 4<br>Participants previously enrolled in Study GS-US-352-1672 will receive momelotinib for approximately 4 years. | Drug: Momelotinib<br>* Momelotinib tablets administered orally once daily<br>* Other names: 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. | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, Post Essential Thrombocythemia Myelofibrosis, Polycythemia Vera, Essential Thrombocythemia, blood disorders