Clinical trial NCT01969838: Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Primary Myelofibrosis
Post-Polycythemia Vera Myelofibrosis
Post-Essential Thrombocythemia Myelofibrosis
Lead sponsor: Sierra Oncology LLC - a GSK company
Sponsor class: INDUSTRY
First posted: 2013-10-25
Enrollment: 432
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is to determine the efficacy of momelotinib (MMB) versus ruxolitinib (RUX) 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 for up to an additional 216 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 participants planning to continue treatment with MMB following the end of the study, the Early Study Drug Discontinuation (ESDD), 30-day, 12-Week, and survival follow-up visits are not required.


Eligibility criteria: Key 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

Key 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

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

Primary outcomes:
measure: Splenic Response Rate at Week 24
timeFrame: Week 24
Secondary outcomes:
measure: Total Symptom Score (TSS) Response Rate at Week 24
timeFrame: Week 24
measure: Rate of Red Blood Cell (RBC) Transfusions in the Double-blind Phase, (the Average Number of RBC Units Transfused Per Month Not Associated With Overt Bleeding)
timeFrame: Baseline to Week 24
measure: 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)
timeFrame: Week 24
measure: RBC Transfusion Dependence Rate at Week 24. (Defined as Having Had at Least 4 Units of RBC Transfusions, or a Hemoglobin Level Below 8 g/dL in 8 Weeks Prior to Week 24 (Excluding Cases Associated With Clinically Overt Bleeding)).
timeFrame: Week 24
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: Escondido
country: United States
state: California
city: Stanford
country: United States
state: California
city: Jacksonville
country: United States
state: Florida
city: Atlanta
country: United States
state: Georgia
city: Chicago
country: United States
state: Illinois
city: Baltimore
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Saint Louis
country: United States
state: Missouri
city: Durham
country: United States
state: North Carolina
city: Seattle
country: United States
state: Washington
city: Darlinghurst
country: Australia
state: New South Wales
city: Parkville
country: Australia
state: New South Wales
city: Saint Leonards
country: Australia
state: New South Wales
city: Brisbane
country: Australia
state: Queensland
city: Herston
country: Australia
state: Queensland
city: Adelaide
country: Australia
state: South Australia
city: Bedford Park
country: Australia
state: South Australia
city: Frankston
country: Australia
state: Victoria
city: Melbourne
country: Australia
state: Victoria
city: Perth
country: Australia
state: Western Australia
city: Wien
country: Austria
state: Vienna
city: Charleroi
country: Belgium
state: Hainaut
city: Antwerp
country: Belgium
city: Leuven
country: Belgium
city: Liege
country: Belgium
city: Pleven
country: Bulgaria
city: Plovdiv
country: Bulgaria
city: Ruse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Varna
country: Bulgaria
city: Edmonton
country: Canada
state: Alberta
city: Vancouver
country: Canada
state: British Columbia
city: Hamilton
country: Canada
state: Ontario
city: Toronto
country: Canada
state: Ontario
city: Hradec Kralove
country: Czechia
state: Vychodocesky KRAJ
city: Brno
country: Czechia
city: Ostrava
country: Czechia
city: Aalborg
country: Denmark
city: Herlev
country: Denmark
city: Toulouse cedex 9
country: France
state: Midi-pyrenees
city: Pierre Bénite Cedex
country: France
state: Rhone-alpes
city: Le Kremlin Bicetre Cedex
country: France
city: Lens
country: France
city: Lille Cedex
country: France
city: Marseille Cedex 9
country: France
city: Nantes cedex 1
country: France
city: Paris
country: France
city: Pessac Cedex
country: France
city: Villejuif Cedex
country: France
city: München
country: Germany
state: Bayern
city: Leipzig
country: Germany
state: Sachsen
city: Dresden
country: Germany
city: Dusseldorf
country: Germany
city: Freiburg
country: Germany
city: Hamburg
country: Germany
city: Mainz
country: Germany
city: Mannheim
country: Germany
city: Budapest
country: Hungary
city: Debrecen
country: Hungary
city: Kaposvár
country: Hungary
city: Afula
country: Israel
city: Ashkelon
country: Israel
city: Haifa
country: Israel
city: Jerusalem
country: Israel
city: Tel Aviv
country: Israel
city: Ogaki City
country: Japan
state: Gifu
city: Kitaku Sapporo
country: Japan
state: Hokkaido
city: Osaka Sayama
country: Japan
state: Osaka
city: Osaka-City
country: Japan
state: Osaka
city: Bunkyo-ku, Tokyo
country: Japan
city: Fukushima City
country: Japan
city: Kumamoto City
country: Japan
city: Matsuyama
country: Japan
city: Okayama
country: Japan
city: Seoul
country: Korea, Republic of
city: Maastricht
country: Netherlands
city: Nijmegen
country: Netherlands
city: Rotterdam
country: Netherlands
city: Utrecht
country: Netherlands
city: Lodz
country: Poland
state: Lodzkie
city: Lublin
country: Poland
state: Lubelskie
city: Kraków
country: Poland
state: Malopolskie
city: Warszawa
country: Poland
state: Mazowiekie
city: Gdansk
country: Poland
state: Pomorskie
city: Poznan
country: Poland
state: Wielkopolskie
city: Bialystok
country: Poland
city: Brzozow
country: Poland
city: Chorzow
country: Poland
city: Arad
country: Romania
city: Brasov
country: Romania
city: Bucuresti
country: Romania
city: Cluj-Napoca
country: Romania
city: Iasi
country: Romania
city: Singapore
country: Singapore
city: Majadahonda
country: Spain
state: Madrid
city: Pamplona
country: Spain
state: Navarra
city: Badalona
country: Spain
city: Barcelona
country: Spain
city: Valencia
country: Spain
city: Zaragoza
country: Spain
city: Lund
country: Sweden
state: Skane
city: Stockholm
country: Sweden
city: Uddevalla
country: Sweden
city: Örebro
country: Sweden
city: Kaohsiung
country: Taiwan
city: Leicester
country: United Kingdom
state: England
city: London
country: United Kingdom
state: England
city: Manchester
country: United Kingdom
state: England
city: Newcastle Upon Tyne
country: United Kingdom
state: England
city: Oxford
country: United Kingdom
state: England
city: Cardiff
country: United Kingdom
state: Wales
city: Northern Ireland
country: United Kingdom
city: Nottingham
country: United Kingdom
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: