Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis

This study is currently recruiting participants.
Verified March 2014 by Gilead Sciences
Information provided by (Responsible Party):
Gilead Sciences Identifier:
First received: October 22, 2013
Last updated: March 26, 2014
Last verified: March 2014

This study is to determine the efficacy of momelotinib (MMB) versus ruxolitinib in participants with primary myelofibrosis (PMF) or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (post-PV/ET MF) who have not yet received treatment with a Janus kinase inhibitor (JAK inhibitor).

Participants will be randomized to receive either MMB or ruxolitinib for 24 weeks during a double-blind treatment phase, after which they will be eligible to receive open-label MMB through Week 168. After discontinuation of study medication, assessments will continue for 12 additional weeks, after which participants will be contacted for survival follow-up approximately every 6 months for up to 5 years from the date of enrollment.

Condition Intervention Phase
Primary Myelofibrosis
Post-Polycythemia Vera Myelofibrosis
Post-Essential Thrombocythemia Myelofibrosis
Drug: Momelotinib
Drug: Ruxolitinib
Drug: Placebo to match momelotinib
Drug: Placebo to match ruxolitinib
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized, Double-blind Active-controlled Study Evaluating Momelotinib vs. Ruxolitinib in Subjects With Primary Myelofibrosis (PMF) or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)

Resource links provided by NLM:

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • Splenic response rate at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Splenic response rate at Week 24 is defined as the proportion of participants achieving a ≥ 35% reduction in spleen volume at Week 24 from baseline as measured by MRI or CT.

Secondary Outcome Measures:
  • Response rate in total symptom score at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Total symptom score (TSS) is defined as the proportion of participants who achieve a ≥ 50% reduction in TSS from baseline to Week 24 as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPNSAF TSS) v2.0 diary.

  • Rate of red blood cell (RBC) transfusion through Week 24 [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    Rate of RBC transfusion is defined as the average number of RBC units per participant per month.

  • RBC transfusion independence rate at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

    RBC transfusion independence is the proportion of participants who are transfusion independent at Week 24, defined as absence of RBC transfusions and no hemoglobin level below 8 g/dL in the prior 12 weeks.


  • RBC transfusion dependence rate at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    RBC transfusion dependence is the proportion of participants who are transfusion dependent at Week 24, defined as at least 4 units of RBC transfusions, or a hemoglobin level below 8 g/dL in the prior 8 weeks.

Estimated Enrollment: 420
Study Start Date: October 2013
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Momelotinib
Participants will receive momelotinib plus placebo to match ruxolitinib.
Drug: Momelotinib
Momelotinib tablet administered orally once daily
Other Names:
  • GS-0387
  • CYT387
Drug: Placebo to match ruxolitinib
Placebo to match ruxolitinib tablets administered orally twice daily
Active Comparator: Ruxolitinib
Participants will receive ruxolitinib plus placebo to match momelotinib.
Drug: Ruxolitinib
Ruxolitinib tablets administered orally twice daily
Drug: Placebo to match momelotinib
Placebo to match momelotinib tablets administered orally once daily


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Palpable splenomegaly at least 5 cm below the left costal margin
  • Confirmed diagnosis of PMF or post-PV/ET MF
  • Requires myelofibrosis therapy, in the opinion of the investigator
  • Classified as high risk OR intermediate-2 risk as defined by the International Prognostic Scoring System (IPSS) for PMF, or intermediate-1 risk (IPSS) associated with symptomatic splenomegaly, hepatomegaly, anemia (hemoglobin < 10.0 g/dL), and/or unresponsive to available therapy
  • Acceptable laboratory assessment obtained within 14 days prior to the first dose of study drug:

    • Absolute neutrophil count (ANC) ≥ 0.75 x 10^9/L in the absence of growth factor in the prior 7 days
    • Platelet Count ≥ 50 x 10^9/L (≥ 100 x 10^9/L if aspartate aminotransferase [AST] or alanine aminotransferase [ALT] is ≥ 2 x the upper limit of the normal range [ULN]) in the absence of platelet transfusion(s) or thrombopoietin mimetics in the prior 7 days
    • Peripheral blood blast count < 10%
    • AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days)
    • Calculated creatinine clearance (CrCL) of ≥ 45 mL/min
    • Direct bilirubin ≤ 2.0 x ULN
  • Life expectancy of > 24 weeks
  • Males and females of childbearing potential must agree to use protocol-specified method(s) of contraception
  • Females who are nursing must agree to discontinue nursing before the first dose of study drug
  • Able to understand and willing to sign the informed consent form

Exclusion Criteria:

  • Prior splenectomy
  • Splenic irradiation within 3 months prior to the first dose of study drug
  • Eligible for allogeneic bone marrow or stem cell transplantation
  • Uncontrolled inter-current illness, per protocol.
  • Known positive status for human immunodeficiency virus (HIV)
  • Chronic active or acute viral hepatitis A, B, or C infection, or a hepatitis B or C carrier
  • Prior use of a JAK1 or JAK2 inhibitor
  • Use of chemotherapy, immunomodulating therapy, biologic therapy, radiation therapy, or investigational therapy within 4 weeks of the first dose of study drug
  • Presence of peripheral neuropathy ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2
  • Unwilling or unable to undergo a magnetic resonance imaging (MRI) or computed tomography (CT) scan
  Contacts and Locations
Please refer to this study by its identifier: NCT01969838

United States, Alabama
Birmingham Hematology and Oncology Associates, LLC Recruiting
Birmingham, Alabama, United States, 35213
Contact: Bobbie Parks    205-599-4929   
Contact: Brittany White    1 (205) 939-7181   
Principal Investigator: Jimmie Harvey, Jr., MD         
United States, California
California Cancer Associates for Research and Excellence (CCARE) Recruiting
Escondido, California, United States, 92025
Contact: Mona Bilawa    760-737-2666   
Principal Investigator: Michael Kosmo, MD         
Cancer Care Associates Recruiting
Fresno, California, United States, 93720
Contact: Cynthia Ho    559-326-1222 ext 157   
Contact: Cherra Brum    1 (559) 326-1222 ext 272   
Principal Investigator: Steven Hager, DO         
North County Oncology Recruiting
Oceanside, California, United States, 92056
Contact: Marina Marinine    760-758-5770 ext 104   
Principal Investigator: Warren Paroly, MD         
Hematology Oncology Medical Group of Orange County, Inc. Recruiting
Orange, California, United States, 92868
Contact: Jennifer Taylor    714-835-1800   
Principal Investigator: Timothy Byun, MD         
Bay Area Cancer Research Group, LLC Recruiting
Pleasant Hill, California, United States, 94523
Contact: Kaimiala Cardines    925-676-3200 ext 108      
Contact: Christiane Raymundo    1 (925) 676-3200 ext 102      
Principal Investigator: Kasra Karamlou         
Stanford Cancer Institute Recruiting
Stanford, California, United States, 94305-5821
Contact: Harshdeep Kaur    650-723-3589   
Principal Investigator: Jason Gotlib, MD         
Wellness Oncology and Hematology Recruiting
West Hills, California, United States, 91307-1486
Contact: Marylen Roldan    818-346-1773   
Contact: Rebecca Hernandez    1 (818) 346-1773   
Principal Investigator: Ashkan Lashkari, MD         
United States, Georgia
Emory University School of Medicine Recruiting
Atlanta, Georgia, United States, 30322
Contact: Wilena Session    404-778-5319   
Principal Investigator: Elliott Winton, MD         
United States, Illinois
University of Chicago Recruiting
Chicago, Illinois, United States, 60637
Contact: Michael Daunov    773-834-2119      
Principal Investigator: Olatoyosi Odenike, MD         
United States, Missouri
Washington University School of Medicine Recruiting
Saint Louis, Missouri, United States, 63110
Contact: Karyn Gordon    314-362-0156   
Contact: Deborah Moore    1 (314) 362-8807   
Principal Investigator: Stephen Oh, MD         
United States, Montana
Montana Cancer Specialists Recruiting
Missoula, Montana, United States, 59802
Contact: Holly Frydenlund    406-329-0349   
Principal Investigator: Patrick Beatty, MD, PhD         
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Stephanie Van Derbur    713-745-4525   
Contact: Sheryl Cooke    1 (713) 745-2623   
Principal Investigator: Srdan Verstovsek, MD         
Sponsors and Collaborators
Gilead Sciences
Study Director: Peter Lee, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences Identifier: NCT01969838     History of Changes
Other Study ID Numbers: GS-US-352-0101, 2013-002707-33
Study First Received: October 22, 2013
Last Updated: March 26, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Australia: Department of Health and Ageing Therapeutic Goods Administration
Canada: Health Canada
Mexico: Federal Commission for Protection Against Health Risks
Singapore: Health Sciences Authority
Taiwan : Food and Drug Administration
South Korea: Korea Food and Drug Administration (KFDA)
Israel: Israeli Health Ministry Pharmaceutical Administration
Russia: Ministry of Health of the Russian Federation
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica

Additional relevant MeSH terms:
Primary Myelofibrosis
Polycythemia Vera
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Blood Coagulation Disorders
Blood Platelet Disorders
Hemorrhagic Disorders processed this record on April 17, 2014