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)

NCT01243944 | Completed Phase 3 Results

• 1 other identifier: CINC424B2301
• Study Type: interventional
• Target: 222
• Locations: 18 countries
• Sites: 102

Brief Summary

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).

Conditions

Polycythemia Vera

Keywords

INCB018424

Outcome Measures

Primary Outcomes (1)

• The Percentage of Participants Achieving a Primary Response at Week 32

  Primary response was defined as having achieved hematocrit control (the absence of phlebotomy eligibility beginning at the Week 8 visit and continuing through Week 32) and Spleen Volume Reduction (a greater than or equal to 35% reduction from baseline in spleen volume at Week 32).

  32 Weeks

Secondary Outcomes (12)

• The Percentage of Participants Achieving a Durable Primary Response at Week 48

  48 Weeks

• The Percentage of Participants Achieving Complete Hematological Remission at Week 32

  32 Weeks

• The Percentage of Participants Who Achieved a Durable Complete Hematological Remission at Week 48

  48 Weeks

• The Percentage of Participants Who Achieved a Durable Hematocrit Control at Week 48

  48 Weeks

• The Percentage of Participants Who Achieved Durable Spleen Volume Reduction at Week 48

  48 Weeks

Study Arms (2)

ruxolitinib tablets

EXPERIMENTAL

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

Drug: ruxolitinib tablets

Best Available Therapy

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.

Other: Best Available Therapy (BAT)

Interventions

ruxolitinib tablets 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

ruxolitinib tablets

Best Available Therapy (BAT) 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.

Also known as: BAT could include:, Hydroxyurea, IFN/PEG-IFN, Pipobroman, Anagrelide, Lenalidomide, Pomalidomide, Observation only

Best Available Therapy

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Incyte Corporation: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (102)

Unknown Facility

Birmingham, Alabama, United States

Location

Unknown Facility

Scottsdale, Arizona, United States

Location

Unknown Facility

Pomona, California, United States

Location

Unknown Facility

Sacramento, California, United States

Location

Unknown Facility

San Diego, California, United States

Location

Unknown Facility

Bridgeport, Connecticut, United States

Location

Unknown Facility

New Haven, Connecticut, United States

Location

Unknown Facility

Boynton Beach, Florida, United States

Location

Unknown Facility

Fort Myers, Florida, United States

Location

Unknown Facility

Jacksonville, Florida, United States

Location

Unknown Facility

Winter Park, Florida, United States

Location

Unknown Facility

Boise, Idaho, United States

Location

Unknown Facility

Chicago, Illinois, United States

Location

Unknown Facility

Lafayette, Louisiana, United States

Location

Unknown Facility

Scarborough, Maine, United States

Location

Unknown Facility

Baltimore, Maryland, United States

Location

Unknown Facility

Columbia, Maryland, United States

Location

Unknown Facility

Southfield, Michigan, United States

Location

Unknown Facility

Jefferson City, Missouri, United States

Location

Unknown Facility

St Louis, Missouri, United States

Location

Unknown Facility

Omaha, Nebraska, United States

Location

Unknown Facility

Morristown, New Jersey, United States

Location

Unknown Facility

Somerville, New Jersey, United States

Location

Unknown Facility

Charleston, South Carolina, United States

Location

Unknown Facility

Greenville, South Carolina, United States

Location

Unknown Facility

Nashville, Tennessee, United States

Location

Unknown Facility

Houston, Texas, United States

Location

Unknown Facility

Seattle, Washington, United States

Location

Unknown Facility

Buenos Aires, Argentina

Location

Unknown Facility

Brisbane, Australia

Location

Unknown Facility

Parkville, Australia

Location

Unknown Facility

Tweed Heads, Australia

Location

Unknown Facility

Antwerp, Belgium

Location

Unknown Facility

Bruges, Belgium

Location

Unknown Facility

Brussels, Belgium

Location

Unknown Facility

Leuven, Belgium

Location

Unknown Facility

Hamilton, Canada

Location

Unknown Facility

Montreal, Canada

Location

Unknown Facility

Toronto, Canada

Location

Unknown Facility

Beijing, China

Location

Unknown Facility

Hangzhou, China

Location

Unknown Facility

Avignon, France

Location

Unknown Facility

Bayonne, France

Location

Unknown Facility

Brest, France

Location

Unknown Facility

Lille, France

Location

Unknown Facility

Nantes, France

Location

Unknown Facility

Paris, France

Location

Unknown Facility

Vandœuvre-lès-Nancy, France

Location

Unknown Facility

Aachen, Germany

Location

Unknown Facility

Berlin, Germany

Location

Unknown Facility

Bonn, Germany

Location

Unknown Facility

Freiburg im Breisgau, Germany

Location

Unknown Facility

Hamburg, Germany

Location

Unknown Facility

Jena, Germany

Location

Unknown Facility

Magdeburg, Germany

Location

Unknown Facility

Mannheim, Germany

Location

Unknown Facility

Minden, Germany

Location

Unknown Facility

München, Germany

Location

Unknown Facility

Ulm, Germany

Location

Unknown Facility

Budapest, Hungary

Location

Unknown Facility

Kecskemét, Hungary

Location

Unknown Facility

Szeged, Hungary

Location

Unknown Facility

Szombathely, Hungary

Location

Unknown Facility

Bari, Italy

Location

Unknown Facility

Bergamo, Italy

Location

Unknown Facility

Bologna, Italy

Location

Unknown Facility

Florence, Italy

Location

Unknown Facility

Milan, Italy

Location

Unknown Facility

Napoli, Italy

Location

Unknown Facility

Orbassano, Italy

Location

Unknown Facility

Pavia, Italy

Location

Unknown Facility

Reggio Calabria, Italy

Location

Unknown Facility

Roma, Italy

Location

Unknown Facility

Varese, Italy

Location

Unknown Facility

Vicenza, Italy

Location

Unknown Facility

Chiba, Japan

Location

Unknown Facility

Chuo-city Yamanashi, Japan

Location

Unknown Facility

Maebashi, Japan

Location

Unknown Facility

Nagoya-city Aichi, Japan

Location

Unknown Facility

Osaka, Japan

Location

Unknown Facility

Tokyo, Japan

Location

Unknown Facility

Enschede, Netherlands

Location

Unknown Facility

Rotterdam, Netherlands

Location

Unknown Facility

Moscow, Russia

Location

Unknown Facility

Saint Petersburg, Russia

Location

Unknown Facility

Seoul, South Korea

Location

Unknown Facility

A Coruña, Spain

Location

Unknown Facility

Barcelona, Spain

Location

Unknown Facility

Las Palmas de Gran Canaria, Spain

Location

Unknown Facility

Madrid, Spain

Location

Unknown Facility

Majadahonda, Spain

Location

Unknown Facility

Málaga, Spain

Location

Unknown Facility

Pamplona, Spain

Location

Unknown Facility

Salamanca, Spain

Location

Unknown Facility

Valencia, Spain

Location

Unknown Facility

Bangkok, Thailand

Location

Unknown Facility

Ankara, Turkey (Türkiye)

Location

Unknown Facility

Istanbul, Turkey (Türkiye)

Location

Unknown Facility

Izmir, Turkey (Türkiye)

Location

Unknown Facility

Bournemouth, United Kingdom

Location

Unknown Facility

Cardiff, United Kingdom

Location

Unknown Facility

London, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 31982039 DERIVED

• 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.

  PMID: 29396713 DERIVED

• 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.

  PMID: 28193568 DERIVED

• 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.

  PMID: 27102499 DERIVED

• 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.

  PMID: 25629741 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Polycythemia Vera

Interventions

ruxolitinib; Hydroxyurea; Pipobroman; anagrelide; Lenalidomide; pomalidomide

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

medinfo@incyte.com

855-463-3463

Study Officials

• Srdan Verstovsek, MD,PhD

  M.D. Anderson Cancer Center

  STUDY DIRECTOR

• Mark Jones, MD

  Incyte Corporation

  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: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: November 17, 2010
• First Posted: November 19, 2010
• Study Start: October 27, 2010
• Primary Completion: January 15, 2014
• Study Completion: February 9, 2018
• Last Updated: March 6, 2019
• Results First Posted: March 6, 2015

Record last verified: 2019-02

Locations

FR (7); BE (4); HU (4); JP (6); ES (9); AR (1); US (28); KR (1); AU (3); IT (12); RU (2); TU (3); GB (3); DE (11); CA (3); NL (2); TH (1); CN (2)