AzTrials
AzTrials

Primary Myelofibrosis (PMF)Phase 3Simplify 2NCT02101268

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

A Phase 3 study testing Momelotinib and Best Available Therapy (BAT) in people with Primary Myelofibrosis (PMF) and Post-polycythemia Vera (Post-PV), run by Sierra Oncology LLC - a GSK company at 48 sites in 8 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Momelotinib and Best Available Therapy (BAT)
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
156 participants
Where
48 sitesin 8 countries
Study dates
19 Jun 2014to 25 Apr 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 22Show fewer
  • ≥ 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)

Who cannot join

  • 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
Show all 11Show fewer
  • 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.

Trial locations and contacts

48 sites in 8 countries.

48 sites in 8 countries

United States13 sites

  • Study site

    Albuquerque, New Mexico

  • Study site

    Atlanta, Georgia

  • Study site

    Baltimore, Maryland

  • Study site

    Cleveland, Ohio

  • Study site

    Durham, North Carolina

  • Study site

    Gainesville, Florida

  • Study site

    Houston, Texas

  • Study site

    Kansas City, Kansas

  • Study site

    Los Angeles, California

  • Study site

    New York, New York

  • Study site

    Pittsburgh, Pennsylvania

  • Study site

    St Louis, Missouri

  • Study site

    Winston-Salem, North Carolina

Other trials in United States

France7 sites

  • Study site

    Lille

  • Study site

    Marseille

  • Study site

    Nantes

  • Study site

    Paris

  • Study site

    Pierre-Bénite

  • Study site

    Toulouse

  • Study site

    Villejuif

Other trials in France

Italy7 sites

  • Study site

    Bologna

  • Study site

    Florence

  • Study site

    Genova

  • Study site

    Milan

  • Study site

    Novara

  • Study site

    Roma

  • Study site

    Varese

Other trials in Italy

Spain6 sites

  • Study site

    Badalona

  • Study site

    Barcelona

  • Study site

    Madrid

  • Study site

    Salamanca

  • Study site

    Valencia

  • Study site

    Zaragoza

Other trials in Spain

Germany4 sites

  • Study site

    Cologne

  • Study site

    Dresden

  • Study site

    Hamburg

  • Study site

    Mannheim

Other trials in Germany

Israel4 sites

  • Study site

    Ashkelon

  • Study site

    Haifa

  • Study site

    Jerusalem

  • Study site

    Tel Aviv

Other trials in Israel

United Kingdom4 sites

  • Study site

    Birmingham, England

  • Study site

    Leeds, England

  • Study site

    Leicester, England

  • Study site

    London, England

Other trials in United Kingdom

Canada3 sites

  • Study site

    Edmonton, Alberta

  • Study site

    Montreal

  • Study site

    Toronto

Other trials in Canada

About this study

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

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 204 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 or until study termination. For those subjects planning to continue treatment with MMB following the end of the study, the End of Treatment, 30-day, 12-Week, and survival follow-up visits are not required.

Being tested
Momelotinib, Best Available Therapy (BAT)
Medical subject headings
Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MomelotinibDrug

    Also called GS-0387, CYT387

    Momelotinib tablet administered orally once daily

  • Best Available Therapy (BAT)Drug

    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.

Study groups in NCT02101268
Study groupRoleWhat they receive
Arm 1: MomelotinibExperimentalParticipants will receive open-label 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 204 weeks.
Receives: Drug: Momelotinib
Arm 2: Best Available Therapy (BAT)Active comparatorParticipants in the BAT treatment arm will receive open-label 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 204 weeks.
Receives: Drug: Best Available Therapy (BAT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Splenic Response Rate at Week 24

    Splenic response rate at Week 24 is defined as the percentage of participants who achieved a spleen volume reduction of ≥ 35% from baseline at the Week 24 assessment as measured by MRI or CT.

    Measured: Week 24

Secondary outcomes (4)

  1. Total Symptom Score (TSS) Response Rate at Week 24

    Total symptom score (TSS) is defined as the percentage of participants who achieved a ≥50% reduction in TSS at Week 24 versus baseline as measured by the modified Myeloproliferative Neoplasm Symptom Assessment Form (MPN-SAF) v2.0 diary. Response rate was calculated using the average of the daily TSS from a consecutive 28-day period prior to Week 24, which had ≥20 daily TSS available.

    The modified MPN-SAF patient-reported outcome instrument consisted of 8 items assessing worst daily incidence of tiredness, filling up quickly, abdominal discomfort, night sweats, itching, bone pain, pain under ribs on left side, and inactivity. Scoring of TSS in this study was based on 7 of these items, (0-70) excluding inactivity. These items assess the impact experienced by the participant in the 24 hours prior to completing the questionnaire. All items are measured using a 0 to 10 Numeric Rating Scale, with 0 corresponding to "Absent" and 10 corresponding to "Worst Imaginable."

    Measured: Week 24

  2. Rate of Red Blood Cell (RBC) Transfusion in the Randomized Treatment Phase, (the Average Number of RBC Units Transfused Per Month Not Associated With Overt Bleeding)

    Rate of RBC transfusion is defined as the average number of RBC units transfused not associated with clinically overt bleeding per subject-month during the randomized treatment Phase.

    Measured: Baseline to Week 24

  3. RBC Transfusion Independence Rate at Week 24, (Defined as Absence of RBC Transfusions and no Hemoglobin Level Below 8 g/dL in the 12 Weeks Prior to Week 24, Excluding Cases Associated With Clinically Overt Bleeding)

    RBC transfusion independence rate is the percentage of participants who achieved transfusion independence at Week 24 (responders). RBC transfusion independence is defined as absence of RBC transfusions and no hemoglobin level below 8 g/dL in the 12 weeks prior to Week 24, excluding cases associated with clinically overt bleeding. Transfusion dependence, (non-responder) is defined as at least 4 units of RBC transfusion, or a Hgb level below 8 g/dL, in the 8 weeks prior to week 24.

    Methods used to assess this outcome measure include collection and recording of any instances of RBC transfusions and collection and recording of any local or central lab hemoglobin measurements

    Measured: Week 24

  4. RBC Transfusion Dependence Rate at Week 24

    RBC transfusion dependence is the percentage 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 8 weeks prior to Week 24, excluding cases associated with clinically overt bleeding.

    Measured: Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Apr 2014 (estimated)
  2. Study start19 Jun 2014
  3. Primary completion28 Jul 2016
  4. Study completion25 Apr 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
156 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02101268
Sponsor's protocol ID
GS-US-352-1214
Other IDs
2013-005007-13
Acronym
Simplify 2
Status last verified
May 2023
First submitted
28 Mar 2014
Last updated
23 May 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Mesa R, Palmer JM, Palandri F, Masarova L, Harrison CN, Mazerolle F, M'hari M, Liu T, Zhang S, Cardellino A, Wang Z, Ellis CE, Patnaik D, Regnault A, LeBlanc TW. Association Between Transfusion Status, Hemoglobin Levels, and Patient-Reported Outcomes in Myelofibrosis: A Post Hoc Clinical Trial Analysis. Cancer Med. 2026 Apr;15(4):e71729. doi: 10.1002/cam4.71729.

    PubMed 41958363

  • Mesa RA, Talpaz M, Mazerolle F, Gorsh B, M'Hari M, Regnault A, Ellis C, Wang Z, Purser M, Liu T, Strouse B, Patnaik D. Time Without Transfusion Reliance (TWiTR): Integrating Survival Quality Into Myelofibrosis Treatment Strategies Based on the Phase 3 SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM Trials. EJHaem. 2025 Jun 18;6(3):e70075. doi: 10.1002/jha2.70075. eCollection 2025 Jun.

    PubMed 40535755

  • Harrison CN, Mesa R, Talpaz M, Gupta V, Gerds AT, Perkins A, Goh YT, Fox ML, McLornan D, Palmer J, Foltz L, Vannucchi A, Koschmieder S, Passamonti F, Lee SE, Ellis C, Strouse B, Gonzalez Carreras FJ, Oh ST. Longitudinal Assessment of Transfusion Intensity in Patients With JAK Inhibitor-Naive or -Experienced Myelofibrosis Treated With Momelotinib. Clin Lymphoma Myeloma Leuk. 2025 Mar;25(3):199-211. doi: 10.1016/j.clml.2024.10.001. Epub 2024 Oct 16.

    PubMed 39516087

  • Harrison CN, Vannucchi AM, Recher C, Passamonti F, Gerds AT, Hernandez-Boluda JC, Yacoub A, Sirhan S, Ellis C, Patel B, Strouse B, Platzbecker U. Momelotinib versus Continued Ruxolitinib or Best Available Therapy in JAK Inhibitor-Experienced Patients with Myelofibrosis and Anemia: Subgroup Analysis of SIMPLIFY-2. Adv Ther. 2024 Sep;41(9):3722-3735. doi: 10.1007/s12325-024-02928-4. Epub 2024 Jul 11.

    PubMed 38990433

  • Verstovsek S, Mesa R, Gupta V, Lavie D, Dubruille V, Cambier N, Platzbecker U, Hus M, Xicoy B, Oh ST, Kiladjian JJ, Vannucchi AM, Gerds A, Egyed M, Mayer J, Sacha T, Kawashima J, Morris M, Huang M, Harrison C. Momelotinib long-term safety and survival in myelofibrosis: integrated analysis of phase 3 randomized controlled trials. Blood Adv. 2023 Jul 25;7(14):3582-3591. doi: 10.1182/bloodadvances.2022009311.

    PubMed 37042865

  • Harrison CN, Vannucchi AM, Platzbecker U, Cervantes F, Gupta V, Lavie D, Passamonti F, Winton EF, Dong H, Kawashima J, Maltzman JD, Kiladjian JJ, Verstovsek S. Momelotinib versus best available therapy in patients with myelofibrosis previously treated with ruxolitinib (SIMPLIFY 2): a randomised, open-label, phase 3 trial. Lancet Haematol. 2018 Feb;5(2):e73-e81. doi: 10.1016/S2352-3026(17)30237-5. Epub 2017 Dec 20.

    PubMed 29275119

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Momelotinib and Best Available Therapy (BAT) in people with Primary Myelofibrosis (PMF) and Post-polycythemia Vera (Post-PV), run by Sierra Oncology LLC - a GSK company at 48 sites in 8 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 22 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 48 sites in United States, France, Italy, Spain, Germany and 3 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Splenic Response Rate at Week 24 (time frame: Week 24). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02101268, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2023.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in