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Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects With Primary Myelofibrosis (MF), Post-polycythemia Vera MF, or Post-essential Thrombocythemia MF (Simplify 2)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT02101268
First received: March 28, 2014
Last updated: May 12, 2017
Last verified: May 2017
  Purpose

This study is to determine the efficacy of momelotinib (MMB) versus best available therapy (BAT) in anemic or thrombocytopenic adults with primary myelofibrosis (PMF), or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (Post-PV/ET MF) who were treated with ruxolitinib as measured by splenic response rate at Week 24 (SRR24).

Participants will be randomized to receive either MMB or BAT for 24 weeks during the randomized treatment phase, after which they will be eligible to receive MMB in an extended treatment phase for up to an additional 168 weeks. 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 (PMF) Post-polycythemia Vera (Post-PV) Post-essential Thrombocythemia Myelofibrosis (Post-ET MF) Drug: Momelotinib Drug: Best Available Therapy (BAT) Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3, Randomized Study To Evaluate the Efficacy of Momelotinib Versus Best Available Therapy in Anemic or Thrombocytopenic Subjects With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis Who Were Treated With Ruxolitinib

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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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.


Enrollment: 156
Actual Study Start Date: June 19, 2014
Estimated Study Completion Date: June 2018
Primary Completion Date: July 28, 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1: Momelotinib
Participants will receive momelotinib for 24 weeks during the randomized treatment phase, after which they will be eligible to receive momelotinib in an extended treatment phase for up to an additional 168 weeks.
Drug: Momelotinib
Momelotinib tablet administered orally once daily
Other Names:
  • GS-0387
  • CYT387
Active Comparator: Arm 2: Best Available Therapy (BAT)
Participants in the BAT treatment arm will receive treatment at doses and schedules determined by the investigator in accordance with standard of care. Therapy may be changed at any time during the study except during the screening period. After completion of the randomized treatment phase, participants will be eligible to receive momelotinib for the duration of the study during the extended treatment phase for up to 168 weeks.
Drug: Best Available Therapy (BAT)
Regimens for BAT may include but are not limited to chemotherapy (eg hydroxyurea), anagrelide, corticosteroid, hematopoietic growth factor, immunomodulating agent, androgen, interferon, and may include no myelofibrosis treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • Palpable splenomegaly at least 5 cm below left costal margin
  • Confirmed diagnosis of PMF in accordance, or Post-PV/ET MF
  • Currently or previously treated with ruxolitinib for PMF or Post-PV/ET MF for at least 28 days, and characterized by

    • Requirement for RBC transfusion while on ruxolitinib treatment, OR
    • Dose adjustment of ruxolitinib to < 20 mg twice daily at start of or during ruxolitinib treatment AND at least one of the following while on ruxolitinib treatment:

      • ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 3 thrombocytopenia, OR
      • ≥ CTCAE Grade 3 anemia, OR
      • ≥ CTCAE Grade 3 hematoma (bleed)
  • High risk OR intermediate-2 risk as defined by Dynamic International Prognostic Scoring System (DIPSS), OR intermediate-1 risk as defined by DIPSS and associated with symptomatic splenomegaly, and/or hepatomegaly
  • If receiving myelofibrosis therapy, must be on a stable dose of the same regimen for at least 2 weeks prior to screen date and through the screening period
  • If not receiving myelofibrosis therapy, must remain off therapy for at least 2 weeks prior to screen date and through the screening period
  • Acceptable laboratory assessments obtained within 14 days prior to Randomization

    • Absolute neutrophil count (ANC) > 0.75 x 10^9/L in the absence of growth factor in the prior 7 days
    • Peripheral blood blast count < 10%
    • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 3 x the upper limit of the normal range (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 of ≥ 45 mL/min
    • Direct bilirubin ≤ 2.0 x ULN
  • Life expectancy > 24 weeks
  • Negative serum pregnancy test for female subjects (unless surgically sterile or greater than two years post-menopausal)
  • 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 MMB
  • Able to understand and willing to sign informed consent form (ICF)

Key Exclusion Criteria:

  • Prior splenectomy
  • Splenic irradiation within 3 months prior to Randomization
  • Use of investigational agent within 28 days prior to Randomization
  • Prior treatment with MMB
  • Hematopoietic growth factor (granulocyte growth factor, erythropoiesis stimulating agent, thrombopoietin mimetic) within 28 days prior to Randomization
  • 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 hepatitis B or C carrier
  • Presence of peripheral neuropathy ≥ CTCAE Grade 2
  • Unwilling or unable to undergo a MRI or CT Scan per study protocol requirements

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02101268

  Show 50 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Gilead Study Director Gilead Sciences
  More Information

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02101268     History of Changes
Other Study ID Numbers: GS-US-352-1214
2013-005007-13 ( EudraCT Number )
Study First Received: March 28, 2014
Last Updated: May 12, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Thrombocytosis
Thrombocythemia, Essential
Primary Myelofibrosis
Polycythemia
Polycythemia Vera
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders

ClinicalTrials.gov processed this record on August 18, 2017