Clinical trial NCT01243944: 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)
Official title: Randomized, Open Label, Multicenter Phase III Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 Tablets Versus Best Available Care (The RESPONSE Trial)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Polycythemia Vera
Keywords: INCB018424
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
Collaborators: name: Novartis Pharmaceuticals
First posted: 2010-11-19
Enrollment: 222
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: The Percentage of Participants Achieving a Primary Response at Week 32
timeFrame: 32 Weeks
Secondary outcomes:
measure: The Percentage of Participants Achieving a Durable Primary Response at Week 48
timeFrame: 48 Weeks
measure: The Percentage of Participants Achieving Complete Hematological Remission at Week 32
timeFrame: 32 Weeks
measure: The Percentage of Participants Who Achieved a Durable Complete Hematological Remission at Week 48
timeFrame: 48 Weeks
measure: The Percentage of Participants Who Achieved a Durable Hematocrit Control at Week 48
timeFrame: 48 Weeks
measure: The Percentage of Participants Who Achieved Durable Spleen Volume Reduction at Week 48
timeFrame: 48 Weeks
measure: Estimated Duration of the Primary Response
timeFrame: Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study
measure: The Percentage of Participants Who Achieved Overall Clinicohematologic Response at Week 32
timeFrame: 32 Weeks
measure: The Percentage of Participants Achieving a Durable Complete or Partial Clinicohematologic Response at Week 48
timeFrame: 48 Weeks
measure: Estimated Duration of the Complete Hematological Remission
timeFrame: Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study
measure: Duration of the Absence of Phlebotomy Eligibility
timeFrame: 256 Weeks
measure: Duration of Reduction in Spleen Volume
timeFrame: 256 Weeks
measure: Duration of The Overall Clinicohematologic Response
timeFrame: 256 Weeks
Other outcomes:
Locations:
city: Birmingham
country: United States
state: Alabama
city: Scottsdale
country: United States
state: Arizona
city: Pomona
country: United States
state: California
city: Sacramento
country: United States
state: California
city: San Diego
country: United States
state: California
city: Bridgeport
country: United States
state: Connecticut
city: New Haven
country: United States
state: Connecticut
city: Boynton Beach
country: United States
state: Florida
city: Fort Myers
country: United States
state: Florida
city: Jacksonville
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Boise
country: United States
state: Idaho
city: Chicago
country: United States
state: Illinois
city: Lafayette
country: United States
state: Louisiana
city: Scarborough
country: United States
state: Maine
city: Baltimore
country: United States
state: Maryland
city: Columbia
country: United States
state: Maryland
city: Southfield
country: United States
state: Michigan
city: Jefferson City
country: United States
state: Missouri
city: Saint Louis
country: United States
state: Missouri
city: Omaha
country: United States
state: Nebraska
city: Morristown
country: United States
state: New Jersey
city: Somerville
country: United States
state: New Jersey
city: Charleston
country: United States
state: South Carolina
city: Greenville
country: United States
state: South Carolina
city: Nashville
country: United States
state: Tennessee
city: Houston
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Buenos Aires
country: Argentina
city: Brisbane
country: Australia
city: Parkville
country: Australia
city: Tweed Heads
country: Australia
city: Antwerp
country: Belgium
city: Brugge
country: Belgium
city: Bruxelles
country: Belgium
city: Leuven
country: Belgium
city: Hamilton
country: Canada
city: Montreal
country: Canada
city: Toronto
country: Canada
city: Beijing
country: China
city: Hangzhou
country: China
city: Avignon
country: France
city: Bayonne
country: France
city: Brest
country: France
city: Lille
country: France
city: Nantes
country: France
city: Paris
country: France
city: Vandœuvre-lès-Nancy
country: France
city: Aachen
country: Germany
city: Berlin
country: Germany
city: Bonn
country: Germany
city: Freiburg
country: Germany
city: Hamburg
country: Germany
city: Jena
country: Germany
city: Magdeburg
country: Germany
city: Mannheim
country: Germany
city: Minden
country: Germany
city: Munchen
country: Germany
city: Ulm
country: Germany
city: Budapest
country: Hungary
city: Kecskemet
country: Hungary
city: Szeged
country: Hungary
city: Szombathely
country: Hungary
city: Bari
country: Italy
city: Bergamo
country: Italy
city: Bologna
country: Italy
city: Firenze
country: Italy
city: Milano
country: Italy
city: Napoli
country: Italy
city: Orbassano
country: Italy
city: Pavia
country: Italy
city: Reggio Calabria
country: Italy
city: Roma
country: Italy
city: Varese
country: Italy
city: Vicenza
country: Italy
city: Chiba
country: Japan
city: Chuo-city Yamanashi
country: Japan
city: Maebashi
country: Japan
city: Nagoya-city Aichi
country: Japan
city: Osaka
country: Japan
city: Tokyo
country: Japan
city: Seoul
country: Korea, Republic of
city: Enschede
country: Netherlands
city: Rotterdam
country: Netherlands
city: Moscow
country: Russian Federation
city: St. Petersburg
country: Russian Federation
city: Barcelona
country: Spain
city: Coruña
country: Spain
city: Las Palmas de Gran Canaria
country: Spain
city: Madrid
country: Spain
city: Majadahonda
country: Spain
city: Malaga
country: Spain
city: Pamplona
country: Spain
city: Salamanca
country: Spain
city: Valencia
country: Spain
city: Bangkok
country: Thailand
city: Ankara
country: Turkey
city: Istanbul
country: Turkey
city: Izmir
country: Turkey
city: Bournemouth
country: United Kingdom
city: Cardiff
country: United Kingdom
city: London
country: United Kingdom
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Srdan Verstovsek, MD,PhD
role: STUDY_DIRECTOR
affiliation: Incyte Corporation
name: Mark Jones, MD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.