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

NCT ID: NCT02101268

Last Updated: 2023-05-23

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

156 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-06-19

Study Completion Date

2019-04-25

Brief Summary

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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.

Detailed Description

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Conditions

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1: Momelotinib

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.

Group Type EXPERIMENTAL

Momelotinib

Intervention Type DRUG

Momelotinib tablet administered orally once daily

Arm 2: Best Available Therapy (BAT)

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.

Group Type ACTIVE_COMPARATOR

Best Available Therapy (BAT)

Intervention Type 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.

Interventions

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Momelotinib

Momelotinib tablet administered orally once daily

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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GS-0387 CYT387

Eligibility Criteria

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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)

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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sierra Oncology LLC - a GSK company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

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Los Angeles, California, United States

Site Status

Gainesville, Florida, United States

Site Status

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

Site Status

Countries

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United States Canada France Germany Israel Italy Spain United Kingdom

References

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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.

Reference Type DERIVED
PMID: 40535755 (View on PubMed)

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.

Reference Type DERIVED
PMID: 39516087 (View on PubMed)

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.

Reference Type DERIVED
PMID: 38990433 (View on PubMed)

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.

Reference Type DERIVED
PMID: 37042865 (View on PubMed)

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.

Reference Type DERIVED
PMID: 29275119 (View on PubMed)

Other Identifiers

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2013-005007-13

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-352-1214

Identifier Type: -

Identifier Source: org_study_id

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