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

NCT02101268 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: GS-US-352-12142013-005007-13
• Study Type: interventional
• Target: 156
• Locations: 8 countries
• Sites: 48

Brief 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 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.

Conditions

Primary Myelofibrosis (PMF); Post-polycythemia Vera (Post-PV); Post-essential Thrombocythemia Myelofibrosis (Post-ET MF)

Outcome Measures

Primary Outcomes (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.

  Week 24

Secondary Outcomes (4)

• Total Symptom Score (TSS) Response Rate at Week 24

  Week 24

• 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)

  Baseline to Week 24

• 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)

  Week 24

• RBC Transfusion Dependence Rate at Week 24

  Week 24

Study Arms (2)

Arm 1: Momelotinib

EXPERIMENTAL

Participants 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.

Drug: Momelotinib

Arm 2: Best Available Therapy (BAT)

ACTIVE COMPARATOR

Participants 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.

Drug: Best Available Therapy (BAT)

Interventions

Momelotinib DRUG

Momelotinib tablet administered orally once daily

Also known as: GS-0387, CYT387

Arm 1: Momelotinib

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.

Arm 2: Best Available Therapy (BAT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Sierra Oncology LLC - a GSK company: lead

Study Sites (48)

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Los Angeles, California, United States

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Gainesville, Florida, United States

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Atlanta, Georgia, United States

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Kansas City, Kansas, United States

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Baltimore, Maryland, United States

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St Louis, Missouri, United States

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Albuquerque, New Mexico, United States

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New York, New York, United States

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Durham, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Cleveland, Ohio, United States

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Pittsburgh, Pennsylvania, United States

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Houston, Texas, United States

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Edmonton, Alberta, Canada

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Montreal, Canada

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Toronto, Canada

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Lille, France

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Marseille, France

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Nantes, France

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Paris, France

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Pierre-Bénite, France

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Toulouse, France

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Villejuif, France

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Cologne, Germany

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Dresden, Germany

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Hamburg, Germany

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Mannheim, Germany

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Ashkelon, Israel

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Haifa, Israel

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Jerusalem, Israel

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Tel Aviv, Israel

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Bologna, Italy

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Florence, Italy

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Genova, Italy

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Milan, Italy

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Novara, Italy

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Roma, Italy

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Varese, Italy

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Badalona, Spain

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Barcelona, Spain

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Madrid, Spain

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Salamanca, Spain

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Valencia, Spain

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Zaragoza, Spain

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Birmingham, England, United Kingdom

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Leeds, England, United Kingdom

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Leicester, England, United Kingdom

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London, England, United Kingdom

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Related Publications (5)

• 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.

  PMID: 40535755 DERIVED

• 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.

  PMID: 39516087 DERIVED

• 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.

  PMID: 38990433 DERIVED

• 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.

  PMID: 37042865 DERIVED

• 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.

  PMID: 29275119 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

Best available therapy could also include the approved JAK inhibitor, ruxolitinib, and 88% of participants in the BAT arm continued to receive ruxolitinib.

Results Point of Contact

• Title: GSK Response Center
• Organization: Sierra Oncology, a GlaxoSmithKline company

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2014
• First Posted: April 2, 2014
• Study Start: June 19, 2014
• Primary Completion: July 28, 2016
• Study Completion: April 25, 2019
• Last Updated: May 23, 2023
• Results First Posted: May 23, 2023

Record last verified: 2023-05

Locations

CA (3); US (13); IL (4); DE (4); FR (7); GB (4); ES (6); IT (7)