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Myelofibrosis With High Molecular Risk MutationsPhase 3ReTHINKNCT02598297

Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations.

A Phase 3 study testing Ruxolitinib in people with Myelofibrosis With High Molecular Risk Mutations, run by Novartis Pharmaceuticals at 110 sites in 25 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ruxolitinib
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
49 participants
Where
110 sitesin 25 countries
Study dates
3 Feb 2016to 23 Oct 2017
Phase
Phase 3

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

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

Trial locations and contacts

110 sites in 25 countries.

110 sites in 25 countries

Germany15 sites

  • Novartis Investigative Site

    Aachen, 52074

  • Novartis Investigative Site

    Bochum, 44787

  • Novartis Investigative Site

    Bonn, 53105

  • Novartis Investigative Site

    Chemnitz, 09113

  • Novartis Investigative Site

    Cologne, 50671

  • Novartis Investigative Site

    Dresden, 01307

  • Novartis Investigative Site

    Essen, 45147

  • Novartis Investigative Site

    Halle S, 06120

  • Novartis Investigative Site

    Heilbronn, 74072

  • Novartis Investigative Site

    Leipzig, 04103

  • Novartis Investigative Site

    Lübeck, Schleswig-Holstein, 23563

  • Novartis Investigative Site

    München, 81241

  • Novartis Investigative Site

    Nordhorn, 48527

  • Novartis Investigative Site

    Rostock, 18057

  • Novartis Investigative Site

    Ulm, 89081

Other trials in Germany

Italy12 sites

  • Novartis Investigative Site

    Bari, BA, 70124

  • Novartis Investigative Site

    Bologna, BO, 40138

  • Novartis Investigative Site

    Brescia, BS, 25123

  • Novartis Investigative Site

    Catania, CT, 95123

  • Novartis Investigative Site

    Florence, FI, 50134

  • Novartis Investigative Site

    Milan, MI, 20122

  • Novartis Investigative Site

    Orbassano, TO, 10043

  • Novartis Investigative Site

    Pavia, PV, 27100

  • Novartis Investigative Site

    Reggio Emilia, RE, 42123

  • Novartis Investigative Site

    Rome, Lazio, 00168

  • Novartis Investigative Site

    Terni, TR, 05100

  • Novartis Investigative Site

    Varese, VA, 21100

Other trials in Italy

Japan10 sites

  • Novartis Investigative Site

    Bunkyo Ku, Tokyo, 113-8431

  • Novartis Investigative Site

    Chūō, Yamanashi, 409-3898

  • Novartis Investigative Site

    Fukuoka, Fukuoka, 812-8582

  • Novartis Investigative Site

    Isehara, Kanagawa, 259-1193

  • Novartis Investigative Site

    Kobe, Hyōgo, 650-0047

  • Novartis Investigative Site

    Maebashi, Gunma, 371 8511

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 453-8511

  • Novartis Investigative Site

    Osaka, 545-8586

  • Novartis Investigative Site

    Shinjuku-ku, Tokyo, 160-0023

  • Novartis Investigative Site

    Suita, Osaka, 565 0871

Other trials in Japan

France9 sites

  • Novartis Investigative Site

    Angers, 49033

  • Novartis Investigative Site

    Bayonne, Bayonne Cedex, 64109

  • Novartis Investigative Site

    Brest, 29200

  • Novartis Investigative Site

    Chambéry, 73011

  • Novartis Investigative Site

    Grenoble, 38043

  • Novartis Investigative Site

    Lille, 59037

  • Novartis Investigative Site

    Nice, 06202

  • Novartis Investigative Site

    Rouen, 76038

  • Novartis Investigative Site

    Vandœuvre-lès-Nancy, 54511

Other trials in France

Greece5 sites

  • Novartis Investigative Site

    Athens, GR, 115 27

  • Novartis Investigative Site

    Athens, 106 76

  • Novartis Investigative Site

    Athens, 115 27

  • Novartis Investigative Site

    Pátrai, 265 00

  • Novartis Investigative Site

    Thessaloniki, GR, 570 10

Other trials in Greece

Israel5 sites

  • Novartis Investigative Site

    Afula, 1834111

  • Novartis Investigative Site

    Haifa, 3525408

  • Novartis Investigative Site

    Jerusalem, 91120

  • Novartis Investigative Site

    Tel Aviv, 6423906

  • Novartis Investigative Site

    Zrifin, 70300

Other trials in Israel

United Kingdom5 sites

  • Novartis Investigative Site

    Edgbaston, Birmingham, B15 2GW

  • Novartis Investigative Site

    Leeds, LS9 7TF

  • Novartis Investigative Site

    London, SE1 9RT

  • Novartis Investigative Site

    Manchester, M20 4BX

  • Novartis Investigative Site

    Westbruy on Trym, Bristol, BS10 5NB

Other trials in United Kingdom

Australia4 sites

  • Novartis Investigative Site

    Concord NSW, New South Wales, 2139

  • Novartis Investigative Site

    Liverpool, New South Wales, 2170

  • Novartis Investigative Site

    Nedlands, Western Australia, 6009

  • Novartis Investigative Site

    Wooloongabba, Queensland, 4102

Other trials in Australia

Sweden4 sites

  • Novartis Investigative Site

    Gothenburg, SE-413 45

  • Novartis Investigative Site

    Huddinge, SE-14186

  • Novartis Investigative Site

    Lund, SE-221 85

  • Novartis Investigative Site

    Uddevalla, 451 80

Other trials in Sweden

Taiwan4 sites

  • Novartis Investigative Site

    Kaohsiung City, 83301

  • Novartis Investigative Site

    Putzu City, Chiayi Hsien, 61363

  • Novartis Investigative Site

    Taipei, 10002

  • Novartis Investigative Site

    Taoyuan, 33305

Other trials in Taiwan

Turkey (Türkiye)4 sites

  • Novartis Investigative Site

    Ankara, 06460

  • Novartis Investigative Site

    Istanbul, 34890

  • Novartis Investigative Site

    Samsun, 55139

  • Novartis Investigative Site

    Talas / Kayseri, 38039

Other trials in Turkey (Türkiye)

Belgium3 sites

  • Novartis Investigative Site

    Antwerp, 2060

  • Novartis Investigative Site

    Leuven, 3000

  • Novartis Investigative Site

    Liège, 4000

Other trials in Belgium

Brazil3 sites

  • Novartis Investigative Site

    São Paulo, São Paulo, 05403 000

  • Novartis Investigative Site

    São Paulo, São Paulo, 08270-070

  • Novartis Investigative Site

    São Paulo, 01236030

Other trials in Brazil

Hungary3 sites

  • Novartis Investigative Site

    Budapest, H 1083

  • Novartis Investigative Site

    Debrecen, 4032

  • Novartis Investigative Site

    Kaposvár, 7400

Other trials in Hungary

Poland3 sites

  • Novartis Investigative Site

    Lodz, 93-513

  • Novartis Investigative Site

    Torun, 87 100

  • Novartis Investigative Site

    Wroclaw, 50 367

Other trials in Poland

Russia3 sites

  • Novartis Investigative Site

    Moscow, 129110

  • Novartis Investigative Site

    Saint Petersburg, 191024

  • Novartis Investigative Site

    Saint Petersburg, 194044

Other trials in Russia

Spain3 sites

  • Novartis Investigative Site

    Cadiz, Andalusia, 11009

  • Novartis Investigative Site

    Madrid, 28041

  • Novartis Investigative Site

    Málaga, Andalusia, 29010

Other trials in Spain

Switzerland3 sites

  • Novartis Investigative Site

    Basel, 4031

  • Novartis Investigative Site

    Sankt Gallen, 9001

  • Novartis Investigative Site

    Zurich, 8091

Other trials in Switzerland

Austria2 sites

  • Novartis Investigative Site

    Salzburg, 5020

  • Novartis Investigative Site

    Vienna, A-1090

Other trials in Austria

Denmark2 sites

  • Novartis Investigative Site

    Aalborg, DK 9000

  • Novartis Investigative Site

    Herlev, DK 2730

Other trials in Denmark

Norway2 sites

  • Novartis Investigative Site

    Bergen, N-5021

  • Novartis Investigative Site

    Loerenskog, NO 1478

Other trials in Norway

Portugal2 sites

  • Novartis Investigative Site

    Faro, 8000-386

  • Novartis Investigative Site

    Porto, 4200-072

Other trials in Portugal

Singapore2 sites

  • Novartis Investigative Site

    Singapore, 119228

  • Novartis Investigative Site

    Singapore, 169608

Other trials in Singapore

Canada1 site

  • Novartis Investigative Site

    Toronto, Ontario, M5G 2M9

Other trials in Canada

Hong Kong1 site

  • Novartis Investigative Site

    Hong Kong

Other trials in Hong Kong

About this study

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

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.

Being tested
Ruxolitinib, Ruxolitinib Placebo
Keywords
Early Myelofibrosis, high molecular risk mutations., Ruxolitinib, INC424, High molecular risk mutations, HMR
Medical subject headings
Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RuxolitinibDrug

    Also called INC424

    5 mg tablet for oral use

  • Ruxolitinib PlaceboDrug

    5 mg placebo tablet for oral use

Study groups in NCT02598297
Study groupRoleWhat they receive
RuxolitinibActive comparatorTwo tablets of ruxolitinib 5 mg were administered orally twice per day.
Receives: Drug: Ruxolitinib
Ruxolitinib PlaceboPlacebo comparatorTwo tablets of 5mg placebo were administered orally twice per day.
Receives: Drug: Ruxolitinib Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: From randomization till disease progression (estimated to be assessed up 48 months)

Secondary outcomes (10)

  1. 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.

    Measured: From randomization till progression (estimated to be assessed up to 48 months)

  2. Percentage Change in Spleen Volume From Baseline

    Change in spleen volume (by MRI/CT) from baseline

    Measured: From baseline and assessed on 12 week intervals until end of treatment (EOT)

  3. 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.

    Measured: From Baseline and assessed every 4 weeks until end of treatment

  4. 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.

    Measured: From Baseline and assessed every 4 weeks until end of treatment

  5. Overall Survival

    To evaluate the effect of ruxolitinib on overall survival

    Measured: Time from randomization to date of death due to any cause (estimated to be assessed up to 48 months).

  6. Plasma Ruxolitinib Concentrations

    Characterize pharmacokinetics (PK)by utilizing a population PK approach.

    Measured: Week 12, Wk 48

  7. 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

    Measured: From date of randomization until second disease progression or death, whichever comes first (estimated to be assessed up to 72 months)

  8. 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.

    Measured: 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

  9. Time to First Progressive Splenomegaly (TTPS)

    Time to first progressive splenomegaly as determined by spleen volume (by Magnetic Resonance Imaging (MRI)/Computed Tomography (CT).

    Measured: From randomization until earliest time to progressive splenomegaly (estimated to be assessed up to 48 months)

  10. Time to First Symptomatic Progression (TTSP)

    Time to first symptomatic progression as determined by Myelofibrosis 7 Item Symptom Scale (MF-7)

    Measured: From randomization until symptomatic progression (MF-7)(estimated to be assessed up to 48 months)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Nov 2015 (estimated)
  2. Study start3 Feb 2016
  3. Primary completion23 Oct 2017
  4. Study completion23 Oct 2017

Why it stopped: Unresolvable inability to recruit the patients.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02598297
Sponsor's protocol ID
CINC424A2353
Other IDs
2014-004928-21, 2014
Acronym
ReTHINK
Status last verified
Jul 2019
First submitted
27 Oct 2015
Last updated
16 Aug 2019
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

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