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

NCT02598297 | Terminated Phase 3 Results DMC

• 2 other identifiers: CINC424A23532014-004928-21
• Study Type: interventional
• Target: 49
• Locations: 24 countries
• Sites: 108

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.

Conditions

Myelofibrosis With High Molecular Risk Mutations

Keywords

Early Myelofibrosis; high molecular risk mutations.; Ruxolitinib; INC424; High molecular risk mutations; HMR

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (10)

• Time to Primary Progression (TTP)

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

• Percentage Change in Spleen Volume From Baseline

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

• Percentage Change in Symptoms From Baseline Using MF-7

  From Baseline and assessed every 4 weeks until end of treatment

• Number of Participants With Specific Subscale Scores (From Baseline) Using EQ-5D

  From Baseline and assessed every 4 weeks until end of treatment

• Overall Survival

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

Study Arms (2)

Ruxolitinib

ACTIVE COMPARATOR

Two tablets of ruxolitinib 5 mg were administered orally twice per day.

Drug: Ruxolitinib

Ruxolitinib Placebo

PLACEBO COMPARATOR

Two tablets of 5mg placebo were administered orally twice per day.

Drug: Ruxolitinib Placebo

Interventions

Ruxolitinib DRUG

5 mg tablet for oral use

Also known as: INC424

Ruxolitinib

Ruxolitinib Placebo DRUG

5 mg placebo tablet for oral use

Ruxolitinib Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

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

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (110)

Novartis Investigative Site

Concord NSW, New South Wales, 2139, Australia

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Novartis Investigative Site

Liverpool, New South Wales, 2170, Australia

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Wooloongabba, Queensland, 4102, Australia

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Nedlands, Western Australia, 6009, Australia

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Salzburg, 5020, Austria

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Vienna, A-1090, Austria

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Antwerp, 2060, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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São Paulo, São Paulo, 05403 000, Brazil

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São Paulo, São Paulo, 08270-070, Brazil

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São Paulo, 01236030, Brazil

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Toronto, Ontario, M5G 2M9, Canada

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Aalborg, DK 9000, Denmark

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Herlev, DK 2730, Denmark

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Bayonne, Bayonne Cedex, 64109, France

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Angers, 49033, France

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Brest, 29200, France

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Chambéry, 73011, France

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Grenoble, 38043, France

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Lille, 59037, France

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Nice, 06202, France

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Rouen, 76038, France

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Vandœuvre-lès-Nancy, 54511, France

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Lübeck, Schleswig-Holstein, 23563, Germany

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Aachen, 52074, Germany

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Bochum, 44787, Germany

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Bonn, 53105, Germany

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Chemnitz, 09113, Germany

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Cologne, 50671, Germany

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Dresden, 01307, Germany

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Essen, 45147, Germany

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Halle S, 06120, Germany

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Heilbronn, 74072, Germany

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Leipzig, 04103, Germany

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München, 81241, Germany

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Nordhorn, 48527, Germany

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Rostock, 18057, Germany

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Ulm, 89081, Germany

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Athens, GR, 115 27, Greece

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Thessaloniki, GR, 570 10, Greece

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Athens, 106 76, Greece

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Athens, 115 27, Greece

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Pátrai, 265 00, Greece

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Hong Kong, Hong Kong

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Budapest, H 1083, Hungary

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Debrecen, 4032, Hungary

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Kaposvár, 7400, Hungary

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Afula, 1834111, Israel

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Haifa, 3525408, Israel

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Jerusalem, 91120, Israel

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Tel Aviv, 6423906, Israel

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Zrifin, 70300, Israel

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Bari, BA, 70124, Italy

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Bologna, BO, 40138, Italy

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Brescia, BS, 25123, Italy

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Catania, CT, 95123, Italy

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Florence, FI, 50134, Italy

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Rome, Lazio, 00168, Italy

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Milan, MI, 20122, Italy

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Pavia, PV, 27100, Italy

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Reggio Emilia, RE, 42123, Italy

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Orbassano, TO, 10043, Italy

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Terni, TR, 05100, Italy

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Varese, VA, 21100, Italy

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Nagoya, Aichi-ken, 453-8511, Japan

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Fukuoka, Fukuoka, 812-8582, Japan

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Maebashi, Gunma, 371 8511, Japan

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Kobe, Hyōgo, 650-0047, Japan

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Isehara, Kanagawa, 259-1193, Japan

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Suita, Osaka, 565 0871, Japan

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Bunkyo Ku, Tokyo, 113-8431, Japan

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Shinjuku-ku, Tokyo, 160-0023, Japan

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Chūō, Yamanashi, 409-3898, Japan

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Osaka, 545-8586, Japan

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Bergen, N-5021, Norway

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Loerenskog, NO 1478, Norway

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Lodz, 93-513, Poland

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Torun, 87 100, Poland

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Wroclaw, 50 367, Poland

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Faro, 8000-386, Portugal

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Porto, 4200-072, Portugal

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Moscow, 129110, Russia

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Saint Petersburg, 191024, Russia

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Saint Petersburg, 194044, Russia

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Singapore, 119228, Singapore

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Singapore, 169608, Singapore

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Cadiz, Andalusia, 11009, Spain

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Málaga, Andalusia, 29010, Spain

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Madrid, 28041, Spain

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Gothenburg, SE-413 45, Sweden

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Huddinge, SE-14186, Sweden

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Lund, SE-221 85, Sweden

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Uddevalla, 451 80, Sweden

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Basel, 4031, Switzerland

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Sankt Gallen, 9001, Switzerland

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Zurich, 8091, Switzerland

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Putzu City, Chiayi Hsien, 61363, Taiwan

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Novartis Investigative Site

Kaohsiung City, 83301, Taiwan

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Taipei, 10002, Taiwan

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Taoyuan District, 33305, Taiwan

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Novartis Investigative Site

Ankara, 06460, Turkey (Türkiye)

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Istanbul, 34890, Turkey (Türkiye)

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Novartis Investigative Site

Samsun, 55139, Turkey (Türkiye)

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Novartis Investigative Site

Talas / Kayseri, 38039, Turkey (Türkiye)

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Novartis Investigative Site

Edgbaston, Birmingham, B15 2GW, United Kingdom

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Novartis Investigative Site

Westbruy on Trym, Bristol, BS10 5NB, United Kingdom

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Novartis Investigative Site

Leeds, LS9 7TF, United Kingdom

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Novartis Investigative Site

London, SE1 9RT, United Kingdom

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Novartis Investigative Site

Manchester, M20 4BX, United Kingdom

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MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2015
• First Posted: November 5, 2015
• Study Start: February 3, 2016
• Primary Completion: October 23, 2017
• Study Completion: October 23, 2017
• Last Updated: August 16, 2019
• Results First Posted: August 16, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will share

Locations

HK (1); RU (3); PL (3); TW (4); GB (5); IT (12); JP (10); SG (2); HU (3); AU (4); FR (9); ES (3); SE (4); BR (3); CA (1); DE (15); BE (3); GR (5); IL (5); NO (2); PT (2); CH (3); DK (2); TU (4)