Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care: (The RESPONSE Trial)

NCT ID: NCT01243944

Last Updated: 2019-03-06

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

222 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-10-27

Study Completion Date

2018-02-09

Brief Summary

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This pivotal phase III trial (CINC424B2301) is designed to compare the efficacy and safety of ruxolitinib (INC424) to Best Available Therapy (BAT) in participants with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea (HU).

Detailed Description

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Conditions

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Polycythemia Vera

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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ruxolitinib tablets

Starting dose of 10 mg BID with individualized dose titration ranging from 5 mg once a day (QD) to 25 mg BID based on safety and efficacy

Group Type EXPERIMENTAL

ruxolitinib tablets

Intervention Type DRUG

Starting dose of 10 mg BID with individualized dose titration ranging from 5 mg QD to 25 mg BID based on safety and efficacy

Best Available Therapy

Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements.

Group Type OTHER

Best Available Therapy (BAT)

Intervention Type OTHER

Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements.

Interventions

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ruxolitinib tablets

Starting dose of 10 mg BID with individualized dose titration ranging from 5 mg QD to 25 mg BID based on safety and efficacy

Intervention Type DRUG

Best Available Therapy (BAT)

Best Available Therapy (BAT) will be selected by the Investigator for each participant. BAT may not include experimental agents (i.e. those not approved for the treatment of any indication) as well as a limited number of other selected drugs in accordance with the protocol-defined requirements.

Intervention Type OTHER

Other Intervention Names

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BAT could include: Hydroxyurea IFN/PEG-IFN Pipobroman Anagrelide Lenalidomide Pomalidomide Observation only

Eligibility Criteria

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Inclusion Criteria

* Participants diagnosed with PV for at least 24 weeks prior to screening according to the 2008 World Health Organization criteria
* Participants resistant to or intolerant of hydroxyurea
* Participants with a phlebotomy requirement
* Participants with splenomegaly (palpable or non-palpable) and a spleen volume, as measured by MRI (or CT in applicable participants ), of greater than or equal to 450 cubic centimeters
* Participants with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

Exclusion Criteria

* Women who are pregnant or nursing
* Participants with inadequate liver or renal function
* Participants with significant bacterial, fungal, parasitic, or viral infection requiring treatment
* Participants with an active malignancy within the past 5 years, excluding specific skin cancers
* Participants with known active hepatitis or HIV positivity
* Participants who have previously received treatment with a JAK inhibitor
* Participants being treated with any investigational agent
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Novartis Pharmaceuticals

INDUSTRY

Sponsor Role collaborator

Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Srdan Verstovsek, MD,PhD

Role: STUDY_DIRECTOR

M.D. Anderson Cancer Center

Mark Jones, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

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Birmingham, Alabama, United States

Site Status

Scottsdale, Arizona, United States

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Pomona, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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Bridgeport, Connecticut, United States

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New Haven, Connecticut, United States

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Boynton Beach, Florida, United States

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Fort Myers, Florida, United States

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Jacksonville, Florida, United States

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Winter Park, Florida, United States

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Boise, Idaho, United States

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Chicago, Illinois, United States

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Lafayette, Louisiana, United States

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Scarborough, Maine, United States

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Baltimore, Maryland, United States

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Columbia, Maryland, United States

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Southfield, Michigan, United States

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Jefferson City, Missouri, United States

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St Louis, Missouri, United States

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Omaha, Nebraska, United States

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Morristown, New Jersey, United States

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Somerville, New Jersey, United States

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Charleston, South Carolina, United States

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Greenville, South Carolina, United States

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Nashville, Tennessee, United States

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Houston, Texas, United States

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Seattle, Washington, United States

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Buenos Aires, , Argentina

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Brisbane, , Australia

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Parkville, , Australia

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Tweed Heads, , Australia

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Antwerp, , Belgium

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Bruges, , Belgium

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Brussels, , Belgium

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Leuven, , Belgium

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Hamilton, , Canada

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Montreal, , Canada

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Toronto, , Canada

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Beijing, , China

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Hangzhou, , China

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Avignon, , France

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Bayonne, , France

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Brest, , France

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Lille, , France

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Nantes, , France

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Paris, , France

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Vandœuvre-lès-Nancy, , France

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Aachen, , Germany

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Berlin, , Germany

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Bonn, , Germany

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Freiburg im Breisgau, , Germany

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Hamburg, , Germany

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Jena, , Germany

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Magdeburg, , Germany

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Mannheim, , Germany

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Minden, , Germany

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München, , Germany

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Ulm, , Germany

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Budapest, , Hungary

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Kecskemét, , Hungary

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Szeged, , Hungary

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Szombathely, , Hungary

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Bari, , Italy

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Bergamo, , Italy

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Bologna, , Italy

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Florence, , Italy

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Milan, , Italy

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Napoli, , Italy

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Orbassano, , Italy

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Pavia, , Italy

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Reggio Calabria, , Italy

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Roma, , Italy

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Varese, , Italy

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Vicenza, , Italy

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Chiba, , Japan

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Chuo-city Yamanashi, , Japan

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Maebashi, , Japan

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Nagoya-city Aichi, , Japan

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Osaka, , Japan

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Tokyo, , Japan

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Enschede, , Netherlands

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Rotterdam, , Netherlands

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Moscow, , Russia

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Saint Petersburg, , Russia

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Seoul, , South Korea

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A Coruña, , Spain

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Barcelona, , Spain

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Las Palmas de Gran Canaria, , Spain

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Madrid, , Spain

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Majadahonda, , Spain

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Málaga, , Spain

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Pamplona, , Spain

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Salamanca, , Spain

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Valencia, , Spain

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Bangkok, , Thailand

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Ankara, , Turkey (Türkiye)

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Istanbul, , Turkey (Türkiye)

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Izmir, , Turkey (Türkiye)

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Bournemouth, , United Kingdom

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Cardiff, , United Kingdom

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London, , United Kingdom

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Countries

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United States Argentina Australia Belgium Canada China France Germany Hungary Italy Japan Netherlands Russia South Korea Spain Thailand Turkey (Türkiye) United Kingdom

References

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Kiladjian JJ, Zachee P, Hino M, Pane F, Masszi T, Harrison CN, Mesa R, Miller CB, Passamonti F, Durrant S, Griesshammer M, Kirito K, Besses C, Moiraghi B, Rumi E, Rosti V, Blau IW, Francillard N, Dong T, Wroclawska M, Vannucchi AM, Verstovsek S. Long-term efficacy and safety of ruxolitinib versus best available therapy in polycythaemia vera (RESPONSE): 5-year follow up of a phase 3 study. Lancet Haematol. 2020 Mar;7(3):e226-e237. doi: 10.1016/S2352-3026(19)30207-8. Epub 2020 Jan 23.

Reference Type DERIVED
PMID: 31982039 (View on PubMed)

Kiladjian JJ, Guglielmelli P, Griesshammer M, Saydam G, Masszi T, Durrant S, Passamonti F, Jones M, Zhen H, Li J, Gadbaw B, Perez Ronco J, Khan M, Verstovsek S. Efficacy and safety of ruxolitinib after and versus interferon use in the RESPONSE studies. Ann Hematol. 2018 Apr;97(4):617-627. doi: 10.1007/s00277-017-3225-1. Epub 2018 Feb 2.

Reference Type DERIVED
PMID: 29396713 (View on PubMed)

Verstovsek S, Harrison CN, Kiladjian JJ, Miller C, Naim AB, Paranagama DC, Habr D, Vannucchi AM. Markers of iron deficiency in patients with polycythemia vera receiving ruxolitinib or best available therapy. Leuk Res. 2017 May;56:52-59. doi: 10.1016/j.leukres.2017.01.032. Epub 2017 Jan 31.

Reference Type DERIVED
PMID: 28193568 (View on PubMed)

Verstovsek S, Vannucchi AM, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Kirito K, Besses C, Hino M, Moiraghi B, Miller CB, Cazzola M, Rosti V, Blau I, Mesa R, Jones MM, Zhen H, Li J, Francillard N, Habr D, Kiladjian JJ. Ruxolitinib versus best available therapy in patients with polycythemia vera: 80-week follow-up from the RESPONSE trial. Haematologica. 2016 Jul;101(7):821-9. doi: 10.3324/haematol.2016.143644. Epub 2016 Apr 21.

Reference Type DERIVED
PMID: 27102499 (View on PubMed)

Vannucchi AM, Kiladjian JJ, Griesshammer M, Masszi T, Durrant S, Passamonti F, Harrison CN, Pane F, Zachee P, Mesa R, He S, Jones MM, Garrett W, Li J, Pirron U, Habr D, Verstovsek S. Ruxolitinib versus standard therapy for the treatment of polycythemia vera. N Engl J Med. 2015 Jan 29;372(5):426-35. doi: 10.1056/NEJMoa1409002.

Reference Type DERIVED
PMID: 25629741 (View on PubMed)

Related Links

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Other Identifiers

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CINC424B2301

Identifier Type: -

Identifier Source: org_study_id

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