Clinical trial NCT02598297: Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations.
Official title: A Randomized, Double Blind, Placebo-controlled, Multicenter, Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Myelofibrosis With High Molecular Risk Mutations
Keywords: Early Myelofibrosis
high molecular risk mutations.
Ruxolitinib
INC424
High molecular risk mutations
HMR
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2015-11-05
Enrollment: 49
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: Myelofibrosis patients with high molecular risk mutations have an intrinsically aggressive disease with increased risk of leukemic transformation and reduced overall survival. As there are no therapies currently established in the subset of high molecular risk patients with early myelofibrosis, the study aimed to evaluate ruxolitinib in this patient population.


Eligibility criteria: Inclusion Criteria:

* Confirmed diagnosis of MF with bone marrow fibrosis of at least Grade 1; irrespective of JAK2 mutational status
* Patients with at least one mutation in one of the five HMR genes (ASXL1, EZH2, SRSF2 and IDH1/2)
* Patients with non-palpable spleen or spleen palpable ≤ 5 cm from the left costal margin to the point of greatest splenic protrusion
* Patients with MF-7 score of ≤ 15, with each individual symptom score of ≤ 3

Exclusion Criteria:

* Patients with prior treatment with ruxolitinib or other JAK inhibitors.

Primary outcomes:
measure: Progression Free Survival (PFS-1)
timeFrame: From randomization till disease progression (estimated to be assessed up 48 months)
Secondary outcomes:
measure: Time to Primary Progression (TTP)
timeFrame: From randomization till progression (estimated to be assessed up to 48 months)
measure: Percentage Change in Spleen Volume From Baseline
timeFrame: From baseline and assessed on 12 week intervals until end of treatment (EOT)
measure: Percentage Change in Symptoms From Baseline Using MF-7
timeFrame: From Baseline and assessed every 4 weeks until end of treatment
measure: Number of Participants With Specific Subscale Scores (From Baseline) Using EQ-5D
timeFrame: From Baseline and assessed every 4 weeks until end of treatment
measure: Overall Survival
timeFrame: Time from randomization to date of death due to any cause (estimated to be assessed up to 48 months).
measure: Plasma Ruxolitinib Concentrations
timeFrame: Week 12, Wk 48
measure: Progression Free Survival (PFS-2)
timeFrame: From date of randomization until second disease progression or death, whichever comes first (estimated to be assessed up to 72 months)
measure: Quality-adjusted Life Years From Baseline
timeFrame: Change from Baseline compared with scheduled study visits at the following intervals every 4 weeks up to week 24, every 8 weeks up to Week 48, every 12 weeks past Wk 48 until End of treatment and 30 day follow up visit
measure: Time to First Progressive Splenomegaly (TTPS)
timeFrame: From randomization until earliest time to progressive splenomegaly (estimated to be assessed up to 48 months)
measure: Time to First Symptomatic Progression (TTSP)
timeFrame: From randomization until symptomatic progression (MF-7)(estimated to be assessed up to 48 months)
Other outcomes:
Locations:
city: Concord NSW
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Liverpool
country: Australia
facility: Novartis Investigative Site
state: New South Wales
city: Wooloongabba
country: Australia
facility: Novartis Investigative Site
state: Queensland
city: Nedlands
country: Australia
facility: Novartis Investigative Site
state: Western Australia
city: Salzburg
country: Austria
facility: Novartis Investigative Site
city: Vienna
country: Austria
facility: Novartis Investigative Site
city: Antwerpen
country: Belgium
facility: Novartis Investigative Site
city: Leuven
country: Belgium
facility: Novartis Investigative Site
city: Liege
country: Belgium
facility: Novartis Investigative Site
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: São Paulo
country: Brazil
facility: Novartis Investigative Site
state: SP
city: Sao Paulo
country: Brazil
facility: Novartis Investigative Site
city: Toronto
country: Canada
facility: Novartis Investigative Site
state: Ontario
city: Aalborg
country: Denmark
facility: Novartis Investigative Site
city: Herlev
country: Denmark
facility: Novartis Investigative Site
city: Bayonne
country: France
facility: Novartis Investigative Site
state: Bayonne Cedex
city: Angers Cedex 1
country: France
facility: Novartis Investigative Site
city: Brest
country: France
facility: Novartis Investigative Site
city: Chambéry Cedex
country: France
facility: Novartis Investigative Site
city: Grenoble
country: France
facility: Novartis Investigative Site
city: Lille Cedex
country: France
facility: Novartis Investigative Site
city: Nice Cedex
country: France
facility: Novartis Investigative Site
city: Rouen Cedex 1
country: France
facility: Novartis Investigative Site
city: Vandoeuvre Les Nancy
country: France
facility: Novartis Investigative Site
city: Luebeck
country: Germany
facility: Novartis Investigative Site
state: Schleswig-holstein
city: Aachen
country: Germany
facility: Novartis Investigative Site
city: Bochum
country: Germany
facility: Novartis Investigative Site
city: Bonn
country: Germany
facility: Novartis Investigative Site
city: Chemnitz
country: Germany
facility: Novartis Investigative Site
city: Dresden
country: Germany
facility: Novartis Investigative Site
city: Essen
country: Germany
facility: Novartis Investigative Site
city: Halle S
country: Germany
facility: Novartis Investigative Site
city: Heilbronn
country: Germany
facility: Novartis Investigative Site
city: Koeln
country: Germany
facility: Novartis Investigative Site
city: Leipzig
country: Germany
facility: Novartis Investigative Site
city: Muenchen
country: Germany
facility: Novartis Investigative Site
city: Nordhorn
country: Germany
facility: Novartis Investigative Site
city: Rostock
country: Germany
facility: Novartis Investigative Site
city: Ulm
country: Germany
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
state: GR
city: Thessaloniki
country: Greece
facility: Novartis Investigative Site
state: GR
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Athens
country: Greece
facility: Novartis Investigative Site
city: Patras
country: Greece
facility: Novartis Investigative Site
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Budapest
country: Hungary
facility: Novartis Investigative Site
city: Debrecen
country: Hungary
facility: Novartis Investigative Site
city: Kaposvar
country: Hungary
facility: Novartis Investigative Site
city: Afula
country: Israel
facility: Novartis Investigative Site
city: Haifa
country: Israel
facility: Novartis Investigative Site
city: Jerusalem
country: Israel
facility: Novartis Investigative Site
city: Tel Aviv
country: Israel
facility: Novartis Investigative Site
city: Zrifin
country: Israel
facility: Novartis Investigative Site
city: Bari
country: Italy
facility: Novartis Investigative Site
state: BA
city: Bologna
country: Italy
facility: Novartis Investigative Site
state: BO
city: Brescia
country: Italy
facility: Novartis Investigative Site
state: BS
city: Catania
country: Italy
facility: Novartis Investigative Site
state: CT
city: Firenze
country: Italy
facility: Novartis Investigative Site
state: FI
city: Roma
country: Italy
facility: Novartis Investigative Site
state: Lazio
city: Milano
country: Italy
facility: Novartis Investigative Site
state: MI
city: Pavia
country: Italy
facility: Novartis Investigative Site
state: PV
city: Reggio Emilia
country: Italy
facility: Novartis Investigative Site
state: RE
city: Orbassano
country: Italy
facility: Novartis Investigative Site
state: TO
city: Terni
country: Italy
facility: Novartis Investigative Site
state: TR
city: Varese
country: Italy
facility: Novartis Investigative Site
state: VA
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Maebashi city
country: Japan
facility: Novartis Investigative Site
state: Gunma
city: Kobe-city
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Isehara
country: Japan
facility: Novartis Investigative Site
state: Kanagawa
city: Suita city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chuo-city
country: Japan
facility: Novartis Investigative Site
state: Yamanashi
city: Osaka
country: Japan
facility: Novartis Investigative Site
city: Bergen
country: Norway
facility: Novartis Investigative Site
city: Loerenskog
country: Norway
facility: Novartis Investigative Site
city: Lodz
country: Poland
facility: Novartis Investigative Site
city: Torun
country: Poland
facility: Novartis Investigative Site
city: Wroclaw
country: Poland
facility: Novartis Investigative Site
city: Faro
country: Portugal
facility: Novartis Investigative Site
city: Porto
country: Portugal
facility: Novartis Investigative Site
city: Moscow
country: Russian Federation
facility: Novartis Investigative Site
city: Saint Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: St Petersburg
country: Russian Federation
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Cadiz
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Malaga
country: Spain
facility: Novartis Investigative Site
state: Andalucia
city: Madrid
country: Spain
facility: Novartis Investigative Site
city: Göteborg
country: Sweden
facility: Novartis Investigative Site
city: Huddinge
country: Sweden
facility: Novartis Investigative Site
city: Lund
country: Sweden
facility: Novartis Investigative Site
city: Uddevalla
country: Sweden
facility: Novartis Investigative Site
city: Basel
country: Switzerland
facility: Novartis Investigative Site
city: St Gallen
country: Switzerland
facility: Novartis Investigative Site
city: Zuerich
country: Switzerland
facility: Novartis Investigative Site
city: Putzu City
country: Taiwan
facility: Novartis Investigative Site
state: Chiayi Hsien
city: Kaohsiung City
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Ankara
country: Turkey
facility: Novartis Investigative Site
city: Istanbul
country: Turkey
facility: Novartis Investigative Site
city: Samsun
country: Turkey
facility: Novartis Investigative Site
city: Talas / Kayseri
country: Turkey
facility: Novartis Investigative Site
city: Edgbaston
country: United Kingdom
facility: Novartis Investigative Site
state: Birmingham
city: Westbruy On Trym
country: United Kingdom
facility: Novartis Investigative Site
state: Bristol
city: Leeds
country: United Kingdom
facility: Novartis Investigative Site
city: London
country: United Kingdom
facility: Novartis Investigative Site
city: Manchester
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References: