NCT01493414

Brief Summary

The primary objective of this study was to collect additional safety of INC424 in patients with Primary Myelofibrosis, Post Polycythemia Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis, who either received prior treatment with commercially available agents or who have never received treatment.

Trial Health

98
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Strong global presence with extensive site network
Enrollment
2,233

participants targeted

Target at P75+ for phase_3

Timeline
Completed

Started Aug 2011

Longer than P75 for phase_3

Geographic Reach
25 countries

273 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 16, 2011

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

December 13, 2011

Completed
3 days until next milestone

First Posted

Study publicly available on registry

December 16, 2011

Completed
5.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 26, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 26, 2017

Completed
2.2 years until next milestone

Results Posted

Study results publicly available

April 26, 2019

Completed
Last Updated

April 26, 2019

Status Verified

October 1, 2018

Enrollment Period

5.5 years

First QC Date

December 13, 2011

Results QC Date

January 26, 2018

Last Update Submit

April 25, 2019

Conditions

Keywords

MyelofibrosisPrimary myelofibrosisPMFPost polycythemia myelofibrosisPPV MFPost-essential thrombocythemia myelofibrosisPET-MFINC424Ruxolitinib

Outcome Measures

Primary Outcomes (1)

  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) up to 5 Years

    An adverse event (AE) is any untoward medical occurrence in a clinical trial participant regardless of causal relationship to study drug and regardless whether study drug has been administered. A serious adverse event (SAE) is any untoward medical occurrence or effect that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect or is medically important due to other reasons than the above mentioned criteria. A non-serious AE is any AE that does not meet the criteria above.

    Baseline up to approximately 5 years

Secondary Outcomes (6)

  • Percentage of Participants With at Least 50% Reduction in Spleen Length

    Baseline up to approximately 5 years

  • Number of Participants With Best Overall Response (BOR) up to 5 Years According to Spleen Length

    Baseline up to approximately 5 years

  • Change in Eastern Cooperative Oncology Group (ECOG) Performance Status From Baseline to Worst Post-baseline ECOG Status up to 5 Years

    Baseline up to approximately 5 years

  • Change in Functional Assessment of Cancer Therapy (FACT-TOI, FACT-G) and FACT-Lymphoma (FACT-Lym) Total Scores Measured at Baseline and Week 48

    Baseline and Week 48

  • Time to First Improvement in FACT-Lym, FACIT-Fatigue Score and ECOG Performance Status

    Baseline up to approximately 5 years

  • +1 more secondary outcomes

Study Arms (1)

INC424

EXPERIMENTAL

5 - 25 mg twice a day (BID)

Drug: INC424

Interventions

INC424DRUG

All patients enrolled into the study will receive INC424 (ruxolitinib). Starting dose is based on baseline platelet counts, with doses ranging from 5 to 20 mg twice a day. No INC424 dose will exceed 25 mg BID orally.

Also known as: Ruxolitinib
INC424

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patients must not be eligible for another ongoing INC424 clinical trial.
  • Patients must be diagnosed with PMF, PPV MF or PET-MF, according to the 2008 revised International Standard Criteria, irrespective of JAK2 mutation status..
  • Patients with PMF requiring therapy must be classified as high risk (3 prognostic factors) OR intermediate risk level 2 (2 prognostic factors, no more), OR intermediate risk level 1 (1 prognostic factor, no more) with an enlarged spleen (assessment to occur at the Screening Visit).
  • The prognostic factors, defined by the International Working Group are:
  • Age \> 65 years;
  • Presence of constitutional symptoms (weight loss, fever, night sweats);
  • Marked anemia (Hgb \< 10g/dL)\*;
  • Leukocytosis (history of white blood cell (WBC) \> 25 x109/L);
  • Circulating blasts \> 1%. \* A hemoglobin value \< 10 g/dL must be demonstrated during the Screening Visit for patients who are not transfusion dependent. Patients receiving regular transfusions of packed red blood cells will be considered to have hemoglobin \< 10 g/dL for the purpose of evaluation of risk factors.
  • Patients with Intermediate-1 disease and splenomegaly must have a palpable spleen measuring 5 cm or greater from the costal margin to the point of greatest splenic protrusion.
  • Patients must have a peripheral blood blast count of \< 10%.
  • Patients with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
  • Fedratinib pretreated patients with documented complete physical examination including full neurologic examination and cardiology assessment, thiamine level testing, and MRI of the brain if indicated based on signs or symptoms. Patients pretreated with fedratinib should have completed or be receiving thiamine supplementation according to the investigator's instructions.

You may not qualify if:

  • Patients eligible for hematopoietic stem cell transplantation (suitable candidate and a suitable donor is available).
  • Patients with history of malignancy in past 3 years except for treated, early-stage squamous or basal cell carcinoma in situ.
  • Impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of oral INC424 (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, small bowel resection).
  • Patients with cardiac disease which in the Investigator's opinion may jeopardize the safety of the patient or the compliance with the protocol.
  • Patients with currently uncontrolled or unstable angina, rapid or paroxysmal atrial fibrillation or recent (approximately 6 months) myocardial infarction or acute coronary syndrome.
  • Patients with clinically significant bacterial, fungal, parasitic or viral infection which require therapy. Patients with acute bacterial infections requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
  • Patients with known active hepatitis A, B, C or who are HIV-positive.
  • Patients with inadequate bone marrow reserve at the Baseline visit as demonstrated by:
  • Absolute neutrophil count (ANC) ≤ 1000/µL.
  • Platelet count \< 50,000/µL without the assistance of growth factors, thrombopoietic factors or platelet transfusions.
  • Patients with any history of platelet counts \< 50,000/µL or ANC \< 500/µL except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason.
  • In the case of ruxolitinib pretreated patients, ruxolitinib primary resistant patients defined as:
  • No spleen reduction within the first 12 weeks after front line therapy with ruxolitinib.
  • AND
  • No reduction in symptoms within the first 12 weeks after first-line treatment with ruxolitinib.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (273)

Novartis Investigative Site

Algiers, Algeria

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Novartis Investigative Site

CABA, Buenos Aires, 1209, Argentina

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CABA, Buenos Aires, C1221ADC, Argentina

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Paraná, Entre Ríos Province, E3100BBJ, Argentina

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Novartis Investigative Site

Buenos Aires, C1114AAN, Argentina

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Novartis Investigative Site

Corrientes, W3410AVV, Argentina

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Córdoba, X5016KEH, Argentina

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Innsbruck, Tyrol, 6020, Austria

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Graz, A-8036, Austria

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Linz, 4010, Austria

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Linz, A-4010, Austria

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Novartis Investigative Site

Salzburg, 5020, Austria

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Novartis Investigative Site

Vienna, 1140, Austria

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Novartis Investigative Site

Vienna, A-1090, Austria

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Novartis Investigative Site

Arlon, Luxembourg, 1210, Belgium

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Antwerp, 2060, Belgium

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Bruges, 8000, Belgium

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Brussels, 1070, Belgium

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Novartis Investigative Site

Brussels, 1090, Belgium

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Novartis Investigative Site

Charleroi, 6000, Belgium

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Novartis Investigative Site

Edegem, 2650, Belgium

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Novartis Investigative Site

Ghent, 9000, Belgium

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Novartis Investigative Site

Hasselt, 3500, Belgium

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Kortrijk, 8500, Belgium

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Leuven, 3000, Belgium

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Novartis Investigative Site

Liège, 4000, Belgium

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Novartis Investigative Site

Roeselare, 8800, Belgium

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Wilrijk, 2610, Belgium

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Novartis Investigative Site

Yvoir, 5530, Belgium

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Goiânia, Goiás, 74605-050, Brazil

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Belo Horizonte, Minas Gerais, 30130-100, Brazil

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Curitiba, Paraná, 80060-900, Brazil

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Rio de Janeiro, Rio de Janeiro, 20.211-030, Brazil

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Porto Alegre, Rio Grande do Sul, 90035-003, Brazil

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Campinas, São Paulo, 13083-970, Brazil

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Ribeirão Preto, São Paulo, 14048-900, Brazil

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São Paulo, São Paulo, 01224-000, Brazil

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São Paulo, São Paulo, 05651-901, Brazil

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São Paulo, São Paulo, 08270-070, Brazil

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Edmonton, Alberta, T6G 1Z2, Canada

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Vancouver, British Columbia, V6Z1Y6, Canada

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Moncton, New Brunswick, E1C 6Z8, Canada

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St. John's, Newfoundland and Labrador, A1B 3V6, Canada

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Halifax, Nova Scotia, B3H 1V7, Canada

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Hamilton, Ontario, L8V 5C2, Canada

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Ottawa, Ontario, K1H 8L6, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Windsor, Ontario, N8W 2X3, Canada

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Montreal, Quebec, H2W 1S6, Canada

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Québec, Quebec, G1J 1Z4, Canada

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Saskatoon, Saskatchewan, S7N 4H4, Canada

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Bogota, Cundinamarca, 111411, Colombia

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Medellín, Colombia

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Brno, Czech Republic, 639 00, Czechia

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Hradec Králové, Czech Republic, 500 05, Czechia

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Prague, Czech Republic, 128 20, Czechia

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Olomouc, 775 20, Czechia

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Mannheim, Baden-Wurttemberg, 68305, Germany

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Aachen, 52074, Germany

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Aschaffenburg, 63739, Germany

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Bamberg, 96049, Germany

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Berlin, 13353, Germany

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Berlin, 14195, Germany

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Bochum, 44787, Germany

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Bonn, 53113, Germany

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Bonn, 53119, Germany

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Bottrop, 46236, Germany

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Bremen, 28177, Germany

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Chemnitz, 09113, Germany

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Cologne, 50671, Germany

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Cologne, 50937, Germany

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Darmstadt, 64283, Germany

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Dortmund, 44263, Germany

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Dresden, 01307, Germany

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Duisburg, 47166, Germany

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Düsseldorf, 40225, Germany

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Erlangen, 91054, Germany

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Essen, 45147, Germany

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Frankfurt, 60389, Germany

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Frankfurt, 60590, Germany

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Frankfurt (Oder), 15236, Germany

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Freiburg im Breisgau, 79106, Germany

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Friedrichshafen, 88045, Germany

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Goslar, 38642, Germany

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Göttingen, D-37075, Germany

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Greifswald, 17475, Germany

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Halle, 06110, Germany

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Hamburg, 20099, Germany

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Hamburg, 20246, Germany

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Hamm, 59063, Germany

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Hanover, 30625, Germany

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Hildesheim, 31135, Germany

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Ingolstadt, 85049, Germany

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Jena, 07740, Germany

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Kiel, D-24116, Germany

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Leer, 26789, Germany

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Leipzig, 04103, Germany

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Magdeburg, 39120, Germany

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Mainz, 55131, Germany

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Marburg, 35037, Germany

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Marburg, 35039, Germany

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Minden, 32429, Germany

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Moers, 47441, Germany

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München, 80331, Germany

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München, 81241, Germany

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München, 81675, Germany

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Nuremberg, 90403, Germany

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Oldenburg, 26133, Germany

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Rostock, 18057, Germany

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Stuttgart, 70376, Germany

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Ulm, 89081, Germany

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Würzburg, 97080, Germany

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Athens, GR, 115 27, Greece

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Athens, GR, GR-106 76, Greece

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Novartis Investigative Site

Athens, GR 11527, Greece

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Novartis Investigative Site

Pátrai, 265 00, Greece

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Budapest, H-1097, Hungary

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Debrecen, H-4032, Hungary

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Kaposvár, 7400, Hungary

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Szeged, H-6720, Hungary

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Szombathely, 9700, Hungary

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Cork, Cork, Ireland

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Afula, 1834111, Israel

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Haifa, 3339419, Israel

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Jerusalem, 9112001, Israel

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Petah Tikva, 49100, Israel

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Ramat Gan, 5266202, Israel

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Tel Aviv, 6423906, Israel

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Alessandria, AL, 15100, Italy

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Ancona, AN, 60126, Italy

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Avellino, AV, 83100, Italy

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Bari, BA, 70124, Italy

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Bergamo, BG, 24128, Italy

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Bologna, BO, 40138, Italy

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Brescia, BS, 25123, Italy

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Cagliari, CA, 09100, Italy

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Cagliari, CA, 09126, Italy

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Catania, CT, 95100, Italy

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Catania, CT, 95124, Italy

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Catanzaro, CZ, 88100, Italy

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Cona, FE, 44100, Italy

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San Giovanni Rotondo, FG, 71013, Italy

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Florence, FI, 50134, Italy

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Genova, GE, 16132, Italy

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Lecce, LE, 73100, Italy

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Monza, MB, 20900, Italy

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Milan, MI, 20122, Italy

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Milan, MI, 20133, Italy

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Milan, MI, 20162, Italy

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Modena, MO, 41100, Italy

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Palermo, PA, 90146, Italy

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Padua, PD, 35128, Italy

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Pescara, PE, 65124, Italy

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Pisa, PI, 56126, Italy

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Pesaro, PU, 61100, Italy

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Pavia, PV, 27100, Italy

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Rionero in Vulture, PZ, 85028, Italy

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Ravenna, RA, 48100, Italy

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Reggio Calabria, RC, 89124, Italy

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Reggio Emilia, RE, 42123, Italy

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Roma, RM, 00128, Italy

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Roma, RM, 00133, Italy

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Roma, RM, 00144, Italy

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Roma, RM, 00152, Italy

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Roma, RM, 00161, Italy

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Roma, RM, 00168, Italy

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Roma, RM, 00185, Italy

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Pagani, SA, 84016, Italy

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Siena, SI, 53100, Italy

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Taranto, TA, 74100, Italy

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Orbassano, TO, 10043, Italy

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Torino, TO, 10126, Italy

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Terni, TR, 05100, Italy

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Treviso, TV, 31100, Italy

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Udine, UD, 33100, Italy

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Varese, VA, 21100, Italy

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Venezia, VE, 30174, Italy

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Vicenza, VI, 36100, Italy

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Verona, VR, 37126, Italy

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Ronciglione, VT, 01100, Italy

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Napoli, 80131, Italy

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Napoli, 80132, Italy

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Napoli, 80136, Italy

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Novara, 28100, Italy

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Pavia, 27100, Italy

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Perugia, 06129, Italy

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Guadalajara, Jalisco, 44280, Mexico

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Mexico City, Mexico City, 06726, Mexico

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Monterrey, Nuevo León, 64020, Mexico

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Hermosillo, Sonora, 83000, Mexico

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Puebla City, 72000, Mexico

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Marrakesh, Morocco

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Gdansk, 80-958, Poland

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Katowice, 40-027, Poland

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Krakow, 31-503, Poland

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Opole, 45-372, Poland

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Torun, 87-100, Poland

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Warsaw, 02-776, Poland

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Coimbra, 3000-075, Portugal

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Faro, 8000-386, Portugal

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Lisbon, 1749-035, Portugal

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Porto, 4099-001, Portugal

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Vila Real, 5000 - 508, Portugal

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Irkutsk, 664079, Russia

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Moscow, 125167, Russia

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Nizhny Novgorod, 603126, Russia

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Novosibirsk, 630051, Russia

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Rostov-on-Don, 344022, Russia

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Saint Petersburg, 191024, Russia

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Saint Petersburg, 197341, Russia

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Jeddah, 21423, Saudi Arabia

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Riyadh, 11426, Saudi Arabia

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Bratislava, 85107, Slovakia

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Soweto, Gauteng, 2013, South Africa

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Cape Town, Western Province, 7801, South Africa

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Johannesburg, 2196, South Africa

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Pretoria, 0001, South Africa

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Pretoria, 0027, South Africa

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Ferrol, A Coruna, 15405, Spain

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Cadiz, Andalusia, 11009, Spain

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Granada, Andalusia, 18014, Spain

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Jaén, Andalusia, 23007, Spain

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Málaga, Andalusia, 29010, Spain

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Seville, Andalusia, 41009, Spain

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Seville, Andalusia, 41013, Spain

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Palma de Mallorca, Balearic Islands, 07120, Spain

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Sabadell, Barcelona, 08208, Spain

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Bilbao, Basque Country, 48013, Spain

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Donostia / San Sebastian, Basque Country, 20080, Spain

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Santander, Cantabria, 39008, Spain

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Burgos, Castille and León, 09005, Spain

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Salamanca, Castille and León, 37007, Spain

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Valladolid, Castille and León, 47012, Spain

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Toledo, Castille-La Mancha, 45071, Spain

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Badalona, Catalonia, 08916, Spain

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Barcelona, Catalonia, 08003, Spain

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Barcelona, Catalonia, 08035, Spain

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Barcelona, Catalonia, 08036, Spain

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Girona, Catalonia, 17007, Spain

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L'Hospitalet de Llobregat, Catalonia, 08907, Spain

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Tarragona, Catalonia, 43005, Spain

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Santiago de Compostela, Galicia, 15706, Spain

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Logroño, La Rioja, 26006, Spain

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Las Palmas de Gran Canaria, Las Palmas de G.C, 35010, Spain

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Alcalá de Henares, Madrid, 28805, Spain

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Majadahonda, Madrid, 28222, Spain

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Pozuelo de Alarcón, Madrid, 28223, Spain

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San Sebastián de los Reyes, Madrid, 28702, Spain

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El Palmar, Murcia, 30120, Spain

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Pamplona, Navarre, 31008, Spain

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Oviedo, Principality of Asturias, 33006, Spain

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San Cristóbal de La Laguna, Santa Cruz De Tenerife, 38320, Spain

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Alicante, Valencia, 03010, Spain

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Valencia, Valencia, 46010, Spain

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Valencia, Valencia, 46026, Spain

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Barakaldo, Vizcaya, 48903, Spain

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Barcelona, 08041, Spain

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Las Palmas de Gran Canaria, 35016, Spain

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Madrid, 28006, Spain

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Novartis Investigative Site

Madrid, 28034, Spain

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Novartis Investigative Site

Madrid, 28040, Spain

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Novartis Investigative Site

Madrid, 28041, Spain

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Novartis Investigative Site

Madrid, 28046, Spain

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Zaragoza, 50009, Spain

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Novartis Investigative Site

Zaragoza, 50015, Spain

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Novartis Investigative Site

Bangkok, 10330, Thailand

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Novartis Investigative Site

Bangkok, 10400, Thailand

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Novartis Investigative Site

Bangkok, 10700, Thailand

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Chiang Mai, 50200, Thailand

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Novartis Investigative Site

Sfax, Tunisie, 3029, Tunisia

Location

Novartis Investigative Site

Sousse, 4000, Tunisia

Location

Novartis Investigative Site

Tunis, 1008, Tunisia

Location

Novartis Investigative Site

Tunis, Tunisia

Location

Related Publications (4)

  • Gupta V, Griesshammer M, Martino B, Foltz L, Tavares R, Al-Ali HK, Giraldo P, Guglielmelli P, Lomaia E, Bouard C, Paley C, Tiwari R, Zor E, Raanani P. Analysis of predictors of response to ruxolitinib in patients with myelofibrosis in the phase 3b expanded-access JUMP study. Leuk Lymphoma. 2021 Apr;62(4):918-926. doi: 10.1080/10428194.2020.1845334. Epub 2020 Nov 19.

  • Al-Ali HK, Griesshammer M, Foltz L, Palumbo GA, Martino B, Palandri F, Liberati AM, le Coutre P, Garcia-Hernandez C, Zaritskey A, Tavares R, Gupta V, Raanani P, Giraldo P, Hanel M, Damiani D, Sacha T, Bouard C, Paley C, Tiwari R, Mannelli F, Vannucchi AM. Primary analysis of JUMP, a phase 3b, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis, including those with low platelet counts. Br J Haematol. 2020 Jun;189(5):888-903. doi: 10.1111/bjh.16462. Epub 2020 Feb 4.

  • Tavares R, Souza CA, Paley C, Bouard C, Tiwari R, Pasquini R. A subgroup analysis of JUMP, a phase IIIb, expanded-access study evaluating the safety and efficacy of ruxolitinib in patients with myelofibrosis in a Brazilian cohort. Hematol Transfus Cell Ther. 2020 Jan-Mar;42(1):46-53. doi: 10.1016/j.htct.2019.01.009. Epub 2019 Apr 25.

  • Al-Ali HK, Griesshammer M, le Coutre P, Waller CF, Liberati AM, Schafhausen P, Tavares R, Giraldo P, Foltz L, Raanani P, Gupta V, Tannir B, Ronco JP, Ghosh J, Martino B, Vannucchi AM. Safety and efficacy of ruxolitinib in an open-label, multicenter, single-arm phase 3b expanded-access study in patients with myelofibrosis: a snapshot of 1144 patients in the JUMP trial. Haematologica. 2016 Sep;101(9):1065-73. doi: 10.3324/haematol.2016.143677. Epub 2016 May 31.

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative DisordersBone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Results Point of Contact

Title
Clinical Disclosure Office
Organization
Novartis Pharmaceuticals

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
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 13, 2011

First Posted

December 16, 2011

Study Start

August 16, 2011

Primary Completion

January 26, 2017

Study Completion

January 26, 2017

Last Updated

April 26, 2019

Results First Posted

April 26, 2019

Record last verified: 2018-10

Locations