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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02598297




Registration number
NCT02598297
Ethics application status
Date submitted
27/10/2015
Date registered
5/11/2015
Date last updated
16/08/2019

Titles & IDs
Public title
Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations.
Scientific 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
Secondary ID [1] 0 0
2014-004928-21
Secondary ID [2] 0 0
CINC424A2353
Universal Trial Number (UTN)
Trial acronym
ReTHINK
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelofibrosis With High Molecular Risk Mutations 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ruxolitinib
Treatment: Drugs - Ruxolitinib Placebo

Active Comparator: Ruxolitinib - Two tablets of ruxolitinib 5 mg were administered orally twice per day.

Placebo Comparator: Ruxolitinib Placebo - Two tablets of 5mg placebo were administered orally twice per day.


Treatment: Drugs: Ruxolitinib
5 mg tablet for oral use

Treatment: Drugs: Ruxolitinib Placebo
5 mg placebo tablet for oral use

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression Free Survival (PFS-1) - Progression free survival (PFS-1) from date of randomization until the occurrence of any of the criteria for disease progression:
Progressive splenomegaly
Circulating peripheral blast counts > 10%
Leukemic transformation
Hb < 10g/dl with absolute decrease of at least 3 g/dl from baseline
White blood cell (WBC) counts > 25 x 103/ µL
MF-7 score = 30
Death from any cause
Timepoint [1] 0 0
From randomization till disease progression (estimated to be assessed up 48 months)
Secondary outcome [1] 0 0
Time to Primary Progression (TTP) - TTP is defined as time from randomization until disease progression as defined for PFS-1 excluding death as an event.
Timepoint [1] 0 0
From randomization till progression (estimated to be assessed up to 48 months)
Secondary outcome [2] 0 0
Percentage Change in Spleen Volume From Baseline - Change in spleen volume (by MRI/CT) from baseline
Timepoint [2] 0 0
From baseline and assessed on 12 week intervals until end of treatment (EOT)
Secondary outcome [3] 0 0
Percentage Change in Symptoms From Baseline Using MF-7 - Percentage change from Baseline in MF-7 total symptom score and 7 individual symptoms at each visit was summarized with descriptive statistics. For this scale, symptoms range from 0 to 10 for the severity experienced within the past 24 hours, with 0 being for absence of symptoms and 10 for worst imaginable symptoms.
Timepoint [3] 0 0
From Baseline and assessed every 4 weeks until end of treatment
Secondary outcome [4] 0 0
Number of Participants With Specific Subscale Scores (From Baseline) Using EQ-5D - EQ-ED5 profiles were summarized at baseline and at each scheduled assessment for each of the 5 dimensions separately (Mobility, self-care, usual activities, pain discomfort, anxiety/depression) Only participants with baseline score and at least one non-missing post-baseline score during the treatment period were included. Percentages were based on all these evaluable participants.
The 5 scores for mobility, self-care, usual activities, pain/discomfort and anxiety/depression are all self-explanatory (eg "I have no problems walking" to "I am unable to walk"), except for the following overall health check, where 100 is the best of health, and 0 is the worst health.
Timepoint [4] 0 0
From Baseline and assessed every 4 weeks until end of treatment
Secondary outcome [5] 0 0
Overall Survival - To evaluate the effect of ruxolitinib on overall survival
Timepoint [5] 0 0
Time from randomization to date of death due to any cause (estimated to be assessed up to 48 months).
Secondary outcome [6] 0 0
Plasma Ruxolitinib Concentrations - Characterize pharmacokinetics (PK)by utilizing a population PK approach.
Timepoint [6] 0 0
Week 12, Wk 48
Secondary outcome [7] 0 0
Progression Free Survival (PFS-2) - PFS-2 assessed by 25% increase over new baseline of PFS-1 in any of the following: ? Progressive splenomegaly ? 25 % increase in MF-7 score with absolute score = 30
Timepoint [7] 0 0
From date of randomization until second disease progression or death, whichever comes first (estimated to be assessed up to 72 months)
Secondary outcome [8] 0 0
Quality-adjusted Life Years From Baseline - EQ-5D-5L (EuroQol-5D-5L, is a standardized instrument for measuring health outcomes, is consists of a descriptive system and a visual analogue scale - scores can be summarized into a single index score that provides a simple measure of health for clinical and economic appraisal ) The EQ-5D-5L health states will be converted into index values (utilities) from which the QALY (Quality - adjusted life years) will be calculated. QALY will be summarized descriptively by treatment arm.
Timepoint [8] 0 0
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
Secondary outcome [9] 0 0
Time to First Progressive Splenomegaly (TTPS) - Time to first progressive splenomegaly as determined by spleen volume (by Magnetic Resonance Imaging (MRI)/Computed Tomography (CT).
Timepoint [9] 0 0
From randomization until earliest time to progressive splenomegaly (estimated to be assessed up to 48 months)
Secondary outcome [10] 0 0
Time to First Symptomatic Progression (TTSP) - Time to first symptomatic progression as determined by Myelofibrosis 7 Item Symptom Scale (MF-7)
Timepoint [10] 0 0
From randomization until symptomatic progression (MF-7)(estimated to be assessed up to 48 months)

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Patients with prior treatment with ruxolitinib or other JAK inhibitors.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s

The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Terminated
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Concord NSW
Recruitment hospital [2] 0 0
Novartis Investigative Site - Liverpool
Recruitment hospital [3] 0 0
Novartis Investigative Site - Wooloongabba
Recruitment hospital [4] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2139 - Concord NSW
Recruitment postcode(s) [2] 0 0
2170 - Liverpool
Recruitment postcode(s) [3] 0 0
4102 - Wooloongabba
Recruitment postcode(s) [4] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
Austria
State/province [1] 0 0
Salzburg
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Austria
State/province [2] 0 0
Vienna
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Belgium
State/province [3] 0 0
Antwerpen
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Belgium
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Leuven
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Belgium
State/province [5] 0 0
Liege
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Brazil
State/province [6] 0 0
SP
Country [7] 0 0
Brazil
State/province [7] 0 0
Sao Paulo
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Canada
State/province [8] 0 0
Ontario
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Denmark
State/province [9] 0 0
Aalborg
Country [10] 0 0
Denmark
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Herlev
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France
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Bayonne Cedex
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France
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Angers Cedex 1
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France
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Brest
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France
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Chambéry Cedex
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France
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Grenoble
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France
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Lille Cedex
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France
State/province [17] 0 0
Nice Cedex
Country [18] 0 0
France
State/province [18] 0 0
Rouen Cedex 1
Country [19] 0 0
France
State/province [19] 0 0
Vandoeuvre Les Nancy
Country [20] 0 0
Germany
State/province [20] 0 0
Schleswig-holstein
Country [21] 0 0
Germany
State/province [21] 0 0
Aachen
Country [22] 0 0
Germany
State/province [22] 0 0
Bochum
Country [23] 0 0
Germany
State/province [23] 0 0
Bonn
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Germany
State/province [24] 0 0
Chemnitz
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Germany
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Dresden
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Germany
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Essen
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Germany
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Halle S
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Germany
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Heilbronn
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Germany
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Koeln
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Germany
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Leipzig
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Germany
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Muenchen
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Germany
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Nordhorn
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Germany
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Rostock
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Germany
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Ulm
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Greece
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GR
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Greece
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Athens
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Greece
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Patras
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Hong Kong
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Hong Kong
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Hungary
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Budapest
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Hungary
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Debrecen
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Hungary
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Kaposvar
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Israel
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Afula
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Israel
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Haifa
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Israel
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Jerusalem
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Israel
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Tel Aviv
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Israel
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Zrifin
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Italy
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BA
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Italy
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BO
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Italy
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BS
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Italy
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CT
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Italy
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FI
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Italy
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Lazio
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Italy
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MI
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Italy
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PV
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Italy
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RE
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Italy
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TO
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Italy
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VA
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Aichi
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Fukuoka
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Gunma
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Hyogo
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Kanagawa
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Osaka
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Tokyo
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Japan
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Yamanashi
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Bergen
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Loerenskog
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Lodz
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Faro
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Porto
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Moscow
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Saint Petersburg
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St Petersburg
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Singapore
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Singapore
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Andalucia
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Huddinge
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Lund
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Uddevalla
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Basel
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Zuerich
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Chiayi Hsien
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Kaohsiung City
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Taipei
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Taiwan
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Taoyuan
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Ankara
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Istanbul
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Samsun
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Talas / Kayseri
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United Kingdom
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Birmingham
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Bristol
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United Kingdom
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Leeds
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London
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United Kingdom
State/province [99] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02598297
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT02598297