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

Sponsor
Sierra Oncology, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02124746
Collaborator
(none)
87
Enrollment
22
Locations
4
Arms
55.2
Actual Duration (Months)
4
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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.

Study Design

Study Type:
Interventional
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 :
Apr 30, 2014
Actual Primary Completion Date :
Dec 6, 2018
Actual Study Completion Date :
Dec 6, 2018

Arms and Interventions

ArmIntervention/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
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    1. 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.

    2. 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.

    3. 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.

    4. 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.

    5. 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).

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1ScottsdaleArizonaUnited States
    2OrangeCaliforniaUnited States
    3StanfordCaliforniaUnited States
    4WhittierCaliforniaUnited States
    5JacksonvilleFloridaUnited States
    6BaltimoreMarylandUnited States
    7BostonMassachusettsUnited States
    8Ann ArborMichiganUnited States
    9RochesterMinnesotaUnited States
    10Saint LouisMissouriUnited States
    11BronxNew YorkUnited States
    12New YorkNew YorkUnited States
    13ClevelandOhioUnited States
    14HoustonTexasUnited States
    15Salt Lake CityUtahUnited States
    16FrankstonVictoriaAustralia
    17ParkvilleVictoriaAustralia
    18TorontoOntarioCanada
    19MontrealQuebecCanada
    20La TroncheFrance
    21ParisFrance
    22MindenGermany

    Sponsors and Collaborators

    • Sierra Oncology, Inc.

    Investigators

    • Study Director: Gilead Study Director, Gilead Sciences

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Sierra Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT02124746
    Other Study ID Numbers:
    • GS-US-352-1154
    • 2013-004476-36
    First Posted:
    Apr 28, 2014
    Last Update Posted:
    Feb 5, 2021
    Last Verified:
    Jan 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Sierra Oncology, Inc.
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment DetailsBenefiting subjects enrolled in 1 of 3 prior momelotinib (MMB) studies (parent studies) for the treatment of MF were included for continued dosing of MMB. Cohort 3 (PV/ET; n=13) was closed and subjects were discontinued due to limited efficacy of MMB in the treatment of PV/ET observed in the parent study. Cohort 3 was excluded from all analyses.
    Pre-assignment Detail
    Arm/Group TitleCohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)Cohort 2 (YM387-II-02/GS-US-352-1154)Cohort 4 (GS-US-352-1672/GS-US-352-1154)
    Arm/Group DescriptionSubjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.
    Period Title: Overall Study
    STARTED302222
    COMPLETED1140
    NOT COMPLETED191822

    Baseline Characteristics

    Arm/Group TitleCohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)Cohort 2 (YM387-II-02/GS-US-352-1154)Cohort 4 (GS-US-352-1672/GS-US-352-1154)Total
    Arm/Group DescriptionSubjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.Total of all reporting groups
    Overall Participants30222274
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    66.0
    64.0
    68.0
    66.5
    Sex: Female, Male (Count of Participants)
    Female
    17
    56.7%
    10
    45.5%
    9
    40.9%
    36
    48.6%
    Male
    13
    43.3%
    12
    54.5%
    13
    59.1%
    38
    51.4%
    Race/Ethnicity, Customized (Count of Participants)
    White
    26
    86.7%
    20
    90.9%
    18
    81.8%
    64
    86.5%
    Black or African American
    0
    0%
    2
    9.1%
    2
    9.1%
    4
    5.4%
    Asian
    2
    6.7%
    0
    0%
    0
    0%
    2
    2.7%
    Hispanic or Latino
    1
    3.3%
    0
    0%
    0
    0%
    1
    1.4%
    Other
    1
    3.3%
    0
    0%
    2
    9.1%
    3
    4.1%
    Transfusion Dependent (at baseline in parent study) (Count of Participants)
    Yes
    7
    23.3%
    7
    31.8%
    22
    100%
    36
    48.6%
    No
    23
    76.7%
    12
    54.5%
    0
    0%
    35
    47.3%
    Missing
    0
    0%
    3
    13.6%
    0
    0%
    3
    4.1%

    Outcome Measures

    1. Primary Outcome
    TitleLong Term Safety and Tolerability as Measured by the Incidence and Severity of Adverse Events and Clinical Laboratory Abnormalities
    DescriptionLong-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 FrameFrom the first dose of momelotinib in the parent study to 30 days following permanent discontinuation of momelotinib in Study GS-US-352-1154.

    Outcome Measure Data

    Analysis Population Description
    It was pre-specified that safety outcomes would be analyzed and summarized by starting dose in Study GS-US-352-1154. Therefore data for this outcome measure are presented for the total subjects enrolled to Study GS-US-352-1154 and not by cohort.
    Arm/Group TitleTotal
    Arm/Group DescriptionAll subjects enrolled to Study GS-US-352-1154
    Measure Participants74
    Subjects with ≥ one AE (any grade)
    73
    243.3%
    Subjects with ≥ one Grade 3 or higher AE
    62
    206.7%
    Subjects with Grade 3 lab toxicity (highest grade)
    36
    120%
    Subjects with Grade 4 lab toxicity (highest grade)
    16
    53.3%
    2. Secondary Outcome
    TitleSplenic Response Rate
    DescriptionThe 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 FrameFrom 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.

    Outcome Measure Data

    Analysis Population Description
    Subjects with splenomegaly >5 cm at baseline in the parent studies who were enrolled in Study GS-US-352-1154 were evaluable for splenic response assessment.
    Arm/Group TitleCohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)Cohort 2 (YM387-II-02/GS-US-352-1154)Cohort 4 (GS-US-352-1672/GS-US-352-1154)Total
    Arm/Group DescriptionSubjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.All subjects enrolled to Study GS-US-352-1154
    Measure Participants25211763
    Count of Participants [Participants]
    20
    66.7%
    19
    86.4%
    6
    27.3%
    45
    60.8%
    3. Secondary Outcome
    TitleDuration of Splenic Response
    DescriptionThe 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 FrameFrom 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.

    Outcome Measure Data

    Analysis Population Description
    Duration of splenic response was assessed for spleen responders who enrolled in Study GS-US-352-1154 only.
    Arm/Group TitleCohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)Cohort 2 (YM387-II-02/GS-US-352-1154)Cohort 4 (GS-US-352-1672/GS-US-352-1154)Total
    Arm/Group DescriptionSubjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.All subjects enrolled to Study GS-US-352-1154
    Measure Participants2019645
    Median (Inter-Quartile Range) [days]
    1704.5
    736.0
    447.5
    990.0
    4. Secondary Outcome
    TitleTransfusion Independence Response Rate
    DescriptionThe 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 FrameFrom baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.

    Outcome Measure Data

    Analysis Population Description
    Subjects who were transfusion dependent at baseline in the parent studies and were enrolled in Study GS-US-352-1154 were evaluable for transfusion independence response.
    Arm/Group TitleCohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)Cohort 2 (YM387-II-02/GS-US-352-1154)Cohort 4 (GS-US-352-1672/GS-US-352-1154)Total
    Arm/Group DescriptionSubjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.All subjects enrolled to Study GS-US-352-1154
    Measure Participants772236
    Count of Participants [Participants]
    7
    23.3%
    5
    22.7%
    16
    72.7%
    28
    37.8%
    5. Secondary Outcome
    TitleDuration of Transfusion Independence Response
    DescriptionThe 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 FrameFrom 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.

    Outcome Measure Data

    Analysis Population Description
    Duration of transfusion independence response was assessed for transfusion independence responders who were enrolled in Study GS-US-352-1154.
    Arm/Group TitleCohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)Cohort 2 (YM387-II-02/GS-US-352-1154)Cohort 4 (GS-US-352-1672/GS-US-352-1154)Total
    Arm/Group DescriptionSubjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.All subjects enrolled to Study GS-US-352-1154
    Measure Participants751628
    Median (Inter-Quartile Range) [days]
    357.0
    114.0
    281.5
    193.5
    6. Secondary Outcome
    TitleAnemia Response Rate
    DescriptionThe 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 FrameFrom baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.

    Outcome Measure Data

    Analysis Population Description
    Subjects who were anemia response-evaluable at baseline in the parent studies and were enrolled in Study GS-US-352-1154 were evaluable for anemia response.
    Arm/Group TitleCohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)Cohort 2 (YM387-II-02/GS-US-352-1154)Cohort 4 (GS-US-352-1672/GS-US-352-1154)Total
    Arm/Group DescriptionSubjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.All subjects enrolled to Study GS-US-352-1154
    Measure Participants18122252
    Count of Participants [Participants]
    13
    43.3%
    6
    27.3%
    16
    72.7%
    35
    47.3%
    7. Secondary Outcome
    TitleDuration of Anemia Response
    DescriptionThe 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 FrameFrom baseline in the parent study until the last assessment in Study GS-US-352-1154, up to 30 days following permanent discontinuation of momelotinib.

    Outcome Measure Data

    Analysis Population Description
    Duration of anemia response was assessed for anemia responders who were enrolled in Study GS-US-352-1154.
    Arm/Group TitleCohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)Cohort 2 (YM387-II-02/GS-US-352-1154)Cohort 4 (GS-US-352-1672/GS-US-352-1154)Total
    Arm/Group DescriptionSubjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.All subjects enrolled to Study GS-US-352-1154
    Measure Participants1361635
    Median (Inter-Quartile Range) [days]
    995.0
    120.0
    281.5
    358.0
    8. Secondary Outcome
    TitleRate of RBC Transfusion
    DescriptionThe average number of RBC units per subject month during the parent study and/or Study GS-US-352-1154.
    Time FrameFrom the first dose of momelotinib in the parent study until the last dose of momelotinib in Study GS-US-352-1154.

    Outcome Measure Data

    Analysis Population Description
    It was pre-specified that safety outcomes would be analyzed and summarized by starting dose in Study GS-US-352-1154. Therefore data for this outcome measure are presented for the total subjects enrolled to Study GS-US-352-1154 and not by cohort.
    Arm/Group TitleTotal
    Arm/Group DescriptionAll subjects enrolled to Study GS-US-352-1154
    Measure Participants74
    RBC Transfusion Rate in Parent Studies
    0.08
    RBC Transfusion Rate in Study GS-US-352-1154
    0.00
    RBC Transfusion Rate Since 1st Dose in ParentStudy
    0.06
    9. Secondary Outcome
    TitleOverall Survival
    DescriptionThe 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 FrameFrom baseline in the parent study until the date of last contact or last response assessment, up to 30 days following permanent discontinuation of momelotinib.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleCohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)Cohort 2 (YM387-II-02/GS-US-352-1154)Cohort 4 (GS-US-352-1672/GS-US-352-1154)Total
    Arm/Group DescriptionSubjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.All subjects enrolled to Study GS-US-352-1154
    Measure Participants30222274
    Median (Full Range) [months]
    NA
    NA
    NA
    NA
    10. Secondary Outcome
    TitleProgression-Free Survival
    DescriptionThe 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 FrameFrom baseline in the parent study until the last response assessment, up to 30 days following permanent discontinuation of momelotinib.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleCohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)Cohort 2 (YM387-II-02/GS-US-352-1154)Cohort 4 (GS-US-352-1672/GS-US-352-1154)Total
    Arm/Group DescriptionSubjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.All subjects enrolled to Study GS-US-352-1154
    Measure Participants30222274
    Median (95% Confidence Interval) [months]
    NA
    NA
    NA
    NA
    11. Secondary Outcome
    TitleLeukemia-Free Survival
    DescriptionThe 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 FrameFrom baseline in the parent study until the date of the last assessment, up to 30 days following permanent discontinuation of momelotinib.

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleCohort 1 (CCL09101/ CCL09101E/ GS-US-352-1154)Cohort 2 (YM387-II-02/GS-US-352-1154)Cohort 4 (GS-US-352-1672/GS-US-352-1154)Total
    Arm/Group DescriptionSubjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study CCL09101/ CCL09101E.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study YM387-II-02.Subjects with PMF, post-PV MF or post-ET MF previously enrolled in parent study GS-US-352-1672.All subjects enrolled to Study GS-US-352-1154
    Measure Participants30222274
    Median (Full Range) [months]
    NA
    NA
    NA
    NA

    Adverse Events

    Time FrameFrom the first dose of momelotinib in the parent study until 30 days after the last dose in Study GS-US-352-1154.
    Adverse Event Reporting Description Treatment-emergent AEs were defined as AEs with onset dates on or after the start of study drug in the parent study and no later than 30 days after permanent discontinuation of study drug, or any AEs leading to premature discontinuation of study drug. It was pre-specified that adverse event data would be analyzed and summarized by starting dose in Study GS-US-352-1154. Therefore adverse event data are presented for the total subjects enrolled to Study GS-US-352-1154 and not by cohort.
    Arm/Group TitleTotal
    Arm/Group DescriptionAll subjects enrolled to Study GS-US-352-1154
    All Cause Mortality
    Total
    Affected / at Risk (%)# Events
    Total8/74 (10.8%)
    Serious Adverse Events
    Total
    Affected / at Risk (%)# Events
    Total49/74 (66.2%)
    Blood and lymphatic system disorders
    Anaemia1/74 (1.4%)
    Febrile neutropenia2/74 (2.7%)
    Neutropenia1/74 (1.4%)
    Thrombocytopenia2/74 (2.7%)
    Cardiac disorders
    Angina pectoris2/74 (2.7%)
    Aortic valve disease1/74 (1.4%)
    Atrial fibrillation1/74 (1.4%)
    Atrial flutter1/74 (1.4%)
    Atrioventricular block1/74 (1.4%)
    Cardiac failure1/74 (1.4%)
    Cardiac failure acute1/74 (1.4%)
    Cardiac failure congestive4/74 (5.4%)
    Cardiomyopathy1/74 (1.4%)
    Myocardial infarction1/74 (1.4%)
    Myocardial ischaemia2/74 (2.7%)
    Palpitations1/74 (1.4%)
    Sinus node dysfunction1/74 (1.4%)
    Ventricular tachycardia1/74 (1.4%)
    Gastrointestinal disorders
    Abdominal pain6/74 (8.1%)
    Ascites1/74 (1.4%)
    Colitis1/74 (1.4%)
    Constipation1/74 (1.4%)
    Diarrhoea1/74 (1.4%)
    Gastrointestinal haemorrhage1/74 (1.4%)
    Haematochezia1/74 (1.4%)
    Mouth haemorrhage1/74 (1.4%)
    Salivary gland enlargement1/74 (1.4%)
    Small intestinal obstruction2/74 (2.7%)
    Varices oesophageal1/74 (1.4%)
    General disorders
    Asthenia2/74 (2.7%)
    Chest pain1/74 (1.4%)
    Death1/74 (1.4%)
    Pain1/74 (1.4%)
    Pyrexia2/74 (2.7%)
    Hepatobiliary disorders
    Cholecystitis chronic1/74 (1.4%)
    Infections and infestations
    Appendicitis2/74 (2.7%)
    Bacterial infection1/74 (1.4%)
    Bronchitis1/74 (1.4%)
    Cellulitis1/74 (1.4%)
    Clostridium difficile colitis1/74 (1.4%)
    Gastroenteritis1/74 (1.4%)
    Gastroenteritis escherichia coli1/74 (1.4%)
    Infection1/74 (1.4%)
    Localised infection1/74 (1.4%)
    Lung infection4/74 (5.4%)
    Peritonitis1/74 (1.4%)
    Pharyngitis1/74 (1.4%)
    Pneumococcal sepsis1/74 (1.4%)
    Pneumonia7/74 (9.5%)
    Pneumonia klebsiella1/74 (1.4%)
    Pneumonia pneumococcal1/74 (1.4%)
    Pyelonephritis1/74 (1.4%)
    Respiratory syncytial virus infection1/74 (1.4%)
    Sepsis3/74 (4.1%)
    Sinusitis bacterial1/74 (1.4%)
    Systemic mycosis1/74 (1.4%)
    Upper respiratory tract infection1/74 (1.4%)
    Urinary tract infection3/74 (4.1%)
    Injury, poisoning and procedural complications
    Craniocerebral injury1/74 (1.4%)
    Fall1/74 (1.4%)
    Subdural haematoma1/74 (1.4%)
    Tendon injury1/74 (1.4%)
    Tibia fracture1/74 (1.4%)
    Investigations
    Blood creatinine increased1/74 (1.4%)
    Ejection fraction decreased1/74 (1.4%)
    Metabolism and nutrition disorders
    Dehydration1/74 (1.4%)
    Hypokalaemia1/74 (1.4%)
    Metabolic acidosis1/74 (1.4%)
    Musculoskeletal and connective tissue disorders
    Arthralgia1/74 (1.4%)
    Back pain1/74 (1.4%)
    Bone pain1/74 (1.4%)
    Muscular weakness1/74 (1.4%)
    Myalgia1/74 (1.4%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenocarcinoma of colon1/74 (1.4%)
    Mantle cell lymphoma1/74 (1.4%)
    Non-hodgkin's lymphoma1/74 (1.4%)
    Ovarian cancer1/74 (1.4%)
    Nervous system disorders
    Cerebral haemorrhage1/74 (1.4%)
    Dizziness1/74 (1.4%)
    Intracranial venous sinus thrombosis1/74 (1.4%)
    Ischaemic stroke1/74 (1.4%)
    Syncope1/74 (1.4%)
    Transient global amnesia1/74 (1.4%)
    Wernicke's encephalopathy1/74 (1.4%)
    Psychiatric disorders
    Delirium1/74 (1.4%)
    Renal and urinary disorders
    Acute kidney injury5/74 (6.8%)
    Haematuria1/74 (1.4%)
    Nephrolithiasis1/74 (1.4%)
    Proteinuria1/74 (1.4%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea3/74 (4.1%)
    Pulmonary embolism3/74 (4.1%)
    Skin and subcutaneous tissue disorders
    Hyperhidrosis1/74 (1.4%)
    Vascular disorders
    Deep vein thrombosis1/74 (1.4%)
    Hypotension2/74 (2.7%)
    Thrombosis1/74 (1.4%)
    Other (Not Including Serious) Adverse Events
    Total
    Affected / at Risk (%)# Events
    Total73/74 (98.6%)
    Blood and lymphatic system disorders
    Anaemia27/74 (36.5%)
    Leukocytosis7/74 (9.5%)
    Leukopenia9/74 (12.2%)
    Neutropenia17/74 (23%)
    Thrombocytopenia28/74 (37.8%)
    Thrombocytosis4/74 (5.4%)
    Cardiac disorders
    Atrial fibrillation4/74 (5.4%)
    Pericardial effusion4/74 (5.4%)
    Sinus bradycardia7/74 (9.5%)
    Ear and labyrinth disorders
    Ear discomfort4/74 (5.4%)
    Eye disorders
    Cataract9/74 (12.2%)
    Dry eye8/74 (10.8%)
    Lacrimation increased4/74 (5.4%)
    Vision blurred7/74 (9.5%)
    Gastrointestinal disorders
    Abdominal pain23/74 (31.1%)
    Abdominal pain upper4/74 (5.4%)
    Constipation19/74 (25.7%)
    Diarrhoea41/74 (55.4%)
    Dyspepsia8/74 (10.8%)
    Gastrooesophageal reflux disease5/74 (6.8%)
    Nausea33/74 (44.6%)
    Vomiting21/74 (28.4%)
    General disorders
    Asthenia5/74 (6.8%)
    Chest pain7/74 (9.5%)
    Chills4/74 (5.4%)
    Fatigue35/74 (47.3%)
    Influenza like illness4/74 (5.4%)
    Oedema peripheral19/74 (25.7%)
    Pain6/74 (8.1%)
    Pyrexia16/74 (21.6%)
    Infections and infestations
    Bronchitis7/74 (9.5%)
    Herpes zoster4/74 (5.4%)
    Influenza8/74 (10.8%)
    Lung infection6/74 (8.1%)
    Sinusitis14/74 (18.9%)
    Upper respiratory tract infection14/74 (18.9%)
    Urinary tract infection23/74 (31.1%)
    Injury, poisoning and procedural complications
    Contusion22/74 (29.7%)
    Fall8/74 (10.8%)
    Foot fracture4/74 (5.4%)
    Investigations
    Activated partial thromboplastin time prolonged5/74 (6.8%)
    Alanine aminotransferase increased19/74 (25.7%)
    Amylase increased12/74 (16.2%)
    Aspartate aminotransferase increased11/74 (14.9%)
    Blood alkaline phosphatase increased5/74 (6.8%)
    Blood bilirubin increased8/74 (10.8%)
    Blood creatinine increased17/74 (23%)
    Blood uric acid increased4/74 (5.4%)
    Electrocardiogram QT prolonged4/74 (5.4%)
    Gamma-glutamyltransferase increased4/74 (5.4%)
    International normalised ratio increased5/74 (6.8%)
    Lipase increased15/74 (20.3%)
    Lymphocyte count decreased4/74 (5.4%)
    Neutrophil count decreased5/74 (6.8%)
    Platelet count decreased11/74 (14.9%)
    Weight decreased8/74 (10.8%)
    Weight increased4/74 (5.4%)
    White blood cell count decreased5/74 (6.8%)
    Metabolism and nutrition disorders
    Decreased appetite10/74 (13.5%)
    Dehydration5/74 (6.8%)
    Hyperglycaemia8/74 (10.8%)
    Hyperkalaemia11/74 (14.9%)
    Hyperuricaemia18/74 (24.3%)
    Hypocalcaemia4/74 (5.4%)
    Hypokalaemia6/74 (8.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia21/74 (28.4%)
    Back pain12/74 (16.2%)
    Bone pain8/74 (10.8%)
    Muscle spasms5/74 (6.8%)
    Muscular weakness8/74 (10.8%)
    Musculoskeletal pain5/74 (6.8%)
    Myalgia6/74 (8.1%)
    Neck pain4/74 (5.4%)
    Pain in extremity18/74 (24.3%)
    Nervous system disorders
    Dizziness28/74 (37.8%)
    Dysgeusia5/74 (6.8%)
    Headache28/74 (37.8%)
    Hypoaesthesia5/74 (6.8%)
    Neuropathy peripheral19/74 (25.7%)
    Paraesthesia5/74 (6.8%)
    Peripheral sensory neuropathy31/74 (41.9%)
    Syncope4/74 (5.4%)
    Psychiatric disorders
    Anxiety4/74 (5.4%)
    Depression7/74 (9.5%)
    Insomnia13/74 (17.6%)
    Renal and urinary disorders
    Acute kidney injury5/74 (6.8%)
    Pollakiuria6/74 (8.1%)
    Proteinuria5/74 (6.8%)
    Urinary retention4/74 (5.4%)
    Respiratory, thoracic and mediastinal disorders
    Cough21/74 (28.4%)
    Dyspnoea29/74 (39.2%)
    Dyspnoea exertional4/74 (5.4%)
    Epistaxis5/74 (6.8%)
    Nasal congestion4/74 (5.4%)
    Oropharyngeal pain7/74 (9.5%)
    Productive cough4/74 (5.4%)
    Sinus congestion4/74 (5.4%)
    Skin and subcutaneous tissue disorders
    Alopecia8/74 (10.8%)
    Night sweats10/74 (13.5%)
    Petechiae4/74 (5.4%)
    Pruritus10/74 (13.5%)
    Rash12/74 (16.2%)
    Skin lesion4/74 (5.4%)
    Skin ulcer4/74 (5.4%)
    Surgical and medical procedures
    Tooth extraction5/74 (6.8%)
    Vascular disorders
    Flushing8/74 (10.8%)
    Haematoma5/74 (6.8%)
    Hypertension14/74 (18.9%)
    Hypotension16/74 (21.6%)

    Limitations/Caveats

    Cohort 3 was discontinued and excluded from the safety and efficacy analyses. The survival analyses were subject to a high level of censoring.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Most restrictive: Site may not present or publish results of Trial without advance written notice of Sponsor or two years after completion of Trial at all participating sites. Site must submit all proposed publications or presentations to Sponsor for review. Sponsor can review communications prior to public release and embargo trial results communications for a period between 75 and 180 days from submission to Sponsor for review. Sponsor has right to request Site remove Confidential Information.

    Results Point of Contact

    Name/TitleDr. Barbara Klencke
    OrganizationSierra Oncology, Inc.
    Phone1-604-558-6536
    Emailbklencke@sierraoncology.com
    Responsible Party:
    Sierra Oncology, Inc.
    ClinicalTrials.gov Identifier:
    NCT02124746
    Other Study ID Numbers:
    • GS-US-352-1154
    • 2013-004476-36
    First Posted:
    Apr 28, 2014
    Last Update Posted:
    Feb 5, 2021
    Last Verified:
    Jan 1, 2021