- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02515630
Momelotinib in Transfusion-Dependent Adults With Primary Myelofibrosis (PMF) or Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)
June 14, 2023 updated by: Sierra Oncology LLC - a GSK company
A Phase 2, Open-label, Translational Biology Study of Momelotinib in Transfusion-Dependent Subjects With Primary Myelofibrosis (PMF) or Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)
This study will evaluate the transfusion independence response rate in transfusion-dependent adults with myelofibrosis after treatment with momelotinib (MMB).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
41
Phase
- Phase 2
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Ontario
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Toronto, Ontario, Canada
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Arizona
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Phoenix, Arizona, United States
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California
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Los Angeles, California, United States
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Orange, California, United States
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Florida
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Jacksonville, Florida, United States
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Maryland
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Baltimore, Maryland, United States
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Michigan
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Ann Arbor, Michigan, United States
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Missouri
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Saint Louis, Missouri, United States
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New York
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Bronx, New York, United States
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New York, New York, United States
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North Carolina
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Durham, North Carolina, United States
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Ohio
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Cleveland, Ohio, United States
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Texas
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Houston, Texas, United States
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
Key Inclusion Criteria:
- Diagnosis of PMF or Post PV/ET-MF
- Requires myelofibrosis therapy, in the opinion of the investigator
- High risk OR intermediate-2 risk defined by dynamic international prognostic scoring system (DIPSS) OR intermediate-1 risk defined by DIPSS and associated with symptomatic splenomegaly and/or hepatomegaly
- Transfusion dependent at baseline, defined as ≥ 4 U red blood cell (RBC) transfusion in the 8 weeks prior to first dose of MMB
Acceptable organ function as evidenced by the following:
- Platelet Count ≥ 50 x 10^9/L
- Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3 x upper limit of normal (ULN) or AST or ALT ≤ 5 x ULN if liver is involved by disease process as judged by the investigator
- Serum creatinine ≤ 2.0 mg/dL or calculated creatinine clearance of ≥ 60 mL/min
- Direct bilirubin ≤ 2.0 x ULN
- Life expectancy of > 24 weeks
- Males and females of childbearing potential who engage in heterosexual intercourse must agree to use protocol specified method(s) of contraception
- Lactating females must agree to discontinue nursing before MMB administration
- Able to understand and willing to sign the informed consent form
Key Exclusion Criteria:
- Prior splenectomy
- Splenic irradiation within 3 months prior to the first dose of MMB
- Prior treatment with MMB
- Known positive status of human immunodeficiency virus (HIV)
- Chronic active or acute viral hepatitis A, B, or C infection (testing required for hepatitis B and C), or hepatitis B or C carrier
- Use of strong cytochrome P450 3A4 (CYP3A4) inducer within 2 weeks prior to the first dose of MMB
- Uncontrolled intercurrent illness per protocol
- Treatment with a Janus kinase (JAK) inhibitor within 21 days of the planned first dose of MMB
- Presence of peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
- Unwilling or unable to undergo a MRI per requirements in the study protocol
- Unwilling to consent to genomics sampling
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Momelotinib
MMB for 24 weeks (± 7 days)
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Momelotinib (MMB) tablet administered orally once daily
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Transfusion Independence Response by Week 24
Time Frame: From baseline to Week 24
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The percentage of subjects who became transfusion independent for ≥ 12 weeks at any time on study.
A subject was considered transfusion independent on study if no RBC transfusion occurred in any 12-week period during the 24-week treatment period.
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From baseline to Week 24
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Transfusion Response Rate by Week 24
Time Frame: From baseline to Week 24
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The percentage of subjects who became transfusion independent for ≥ 8 weeks, defined as no RBC transfusions for at least an 8-week period at any time on study.
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From baseline to Week 24
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Splenic Response Rate at Week 24
Time Frame: Measured at Week 24
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The percentage of subjects who achieved a ≥ 35% reduction in spleen volume from baseline as measured by MRI at Week 24.
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Measured at Week 24
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Response Rate in Total Symptom Score (TSS) at Week 24
Time Frame: Measured at Week 24
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The percentage of subjects achieving a ≥ 50% reduction from baseline in TSS at Week 24, as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) diary.
Total symptom score was assessed using the modified MPN-SAF TSS Version 2, an 8-item questionnaire developed to assess symptom burden and quality of life in patients with MPN.
The modified MPN-SAF TSS contained 8 questions, 7 of which were summed to generate the score (the included questions related to tiredness, early satiety, abdominal discomfort, night sweats, itching, bone pain, and pain under the ribs on the left side).
Each question is scored on a scale of 0-10, where higher numbers indicate more severe symptoms.
For this study, the TSS scale ranges from 0 to 70.
The questionnaire was completed daily on an electronic diary device.
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Measured at Week 24
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Change in Markers of Iron Metabolism and Anemia - Change From Baseline in Hepcidin Daily Change
Time Frame: At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24
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Hepcidin daily change (in nM) was calculated as the predose value subtracted from the 6 hours postdose value at each study visit.
Daily hepcidin change at the baseline visit was the difference between 2 values obtained 6 hours apart.
No momelotinib was administered on that day.
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At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Trough Hepcidin
Time Frame: At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24
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Median hepcidin at trough was assessed predose at each study visit.
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At baseline, Day 1, Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Serum Iron
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
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Percent change from baseline in serum iron, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Hemoglobin
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
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Percent change from baseline in hemoglobin, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Total Iron Binding Capacity
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
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Percent change from baseline in total iron binding capacity, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Reticulocytes
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
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Percent change from baseline in reticulocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Reticulocytes/Erythrocytes%
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
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Percent change from baseline in reticulocytes/erythrocytes%, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Erythropoietin
Time Frame: At Weeks 8 and 20
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Percent change in erythropoietin at Weeks 8 and 20.
The baseline erythropoietin value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 8 and 20
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Change in Markers of Iron Metabolism and Anemia - Erythrocytes
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
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Percent change from baseline in erythrocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Hematocrit
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
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Percent change from baseline in hematocrit, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Ferritin
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
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Percent change from baseline in ferritin, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Soluble Transferrin Receptor
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
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Percent change from baseline in soluble transferrin receptor, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Transferrin Saturation
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
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Percent change from baseline in transferrin saturation, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Unsaturated Iron Binding Capacity
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
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Percent change from baseline in unsaturated iron binding capacity, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Platelets
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
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Percent change from baseline in platelets, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Leukocytes
Time Frame: At Weeks 2, 4, 8, 12, 16, 20 and 24
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Percent change from baseline in leukocytes, where the baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 4, 8, 12, 16, 20 and 24
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Change in Markers of Iron Metabolism and Anemia - Blasts
Time Frame: At Weeks 2 and 4
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Change from baseline in % blasts at Weeks 2 and 4. The baseline % blasts value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2 and 4
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Change in Liver Iron Content
Time Frame: Measured at Week 24
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Percent change from baseline in liver iron content assessed by MRI.
The baseline value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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Measured at Week 24
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Change in Pharmacodynamics Biomarker - pSTAT3
Time Frame: On Day 1 and at Weeks 4 and 24
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Percent change in %pSTAT stimulated CD3+/4+ T cell at Day 1 (postdose), Week 4 and Week 24.
The baseline value is defined as the last predose value from the baseline period prior to or on the date of first dose of momelotinib administration (Day 1 predose).
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On Day 1 and at Weeks 4 and 24
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Change in Pharmacodynamics Biomarker - pSTAT3/tSTAT3 Ratio
Time Frame: On Day 1 and at Weeks 4 and 24
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Percent change in %pSTAT/%tSTAT Stimulated CD3+/4+ T cell ratio at Day 1 (postdose), Week 4 and Week 24.
The baseline value is defined as the last predose value from the baseline period prior to or on the date of first dose of momelotinib administration (Day 1 predose).
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On Day 1 and at Weeks 4 and 24
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Change in Inflammatory Markers - C-Reactive Protein (CRP)
Time Frame: At Weeks 2, 12 and 24
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Percent change in C-reactive protein at Weeks 2, 12 and 24.
The baseline C-reactive protein value is defined as the last value from the baseline period prior to or on the date of first dose of momelotinib administration (Baseline visit).
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At Weeks 2, 12 and 24
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
January 29, 2016
Primary Completion (Actual)
July 18, 2017
Study Completion (Actual)
August 15, 2017
Study Registration Dates
First Submitted
August 3, 2015
First Submitted That Met QC Criteria
August 3, 2015
First Posted (Estimated)
August 5, 2015
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
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-352-1672
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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