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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01243944




Registration number
NCT01243944
Ethics application status
Date submitted
17/11/2010
Date registered
19/11/2010
Date last updated
6/03/2019

Titles & IDs
Public title
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)
Scientific 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)
Secondary ID [1] 0 0
CINC424B2301
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Polycythemia Vera 0 0
Condition category
Condition code
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - ruxolitinib tablets
Other interventions - Best Available Therapy (BAT)

Experimental: 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

Other: 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.


Treatment: Drugs: 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

Other interventions: 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 code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
The Percentage of Participants Achieving a Primary Response at Week 32
Timepoint [1] 0 0
32 Weeks
Secondary outcome [1] 0 0
The Percentage of Participants Achieving a Durable Primary Response at Week 48
Timepoint [1] 0 0
48 Weeks
Secondary outcome [2] 0 0
The Percentage of Participants Achieving Complete Hematological Remission at Week 32
Timepoint [2] 0 0
32 Weeks
Secondary outcome [3] 0 0
The Percentage of Participants Who Achieved a Durable Complete Hematological Remission at Week 48
Timepoint [3] 0 0
48 Weeks
Secondary outcome [4] 0 0
The Percentage of Participants Who Achieved a Durable Hematocrit Control at Week 48
Timepoint [4] 0 0
48 Weeks
Secondary outcome [5] 0 0
The Percentage of Participants Who Achieved Durable Spleen Volume Reduction at Week 48
Timepoint [5] 0 0
48 Weeks
Secondary outcome [6] 0 0
Estimated Duration of the Primary Response
Timepoint [6] 0 0
Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study
Secondary outcome [7] 0 0
The Percentage of Participants Who Achieved Overall Clinicohematologic Response at Week 32
Timepoint [7] 0 0
32 Weeks
Secondary outcome [8] 0 0
The Percentage of Participants Achieving a Durable Complete or Partial Clinicohematologic Response at Week 48
Timepoint [8] 0 0
48 Weeks
Secondary outcome [9] 0 0
Estimated Duration of the Complete Hematological Remission
Timepoint [9] 0 0
Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study
Secondary outcome [10] 0 0
Duration of the Absence of Phlebotomy Eligibility
Timepoint [10] 0 0
256 Weeks
Secondary outcome [11] 0 0
Duration of Reduction in Spleen Volume
Timepoint [11] 0 0
256 Weeks
Secondary outcome [12] 0 0
Duration of The Overall Clinicohematologic Response
Timepoint [12] 0 0
256 Weeks

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
27/10/2010
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
9/02/2018
Sample size
Target
Accrual to date
Final
222
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Brisbane
Recruitment hospital [2] 0 0
- Parkville
Recruitment hospital [3] 0 0
- Tweed Heads
Recruitment postcode(s) [1] 0 0
- Brisbane
Recruitment postcode(s) [2] 0 0
- Parkville
Recruitment postcode(s) [3] 0 0
- Tweed Heads
Recruitment outside Australia
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United States of America
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Alabama
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Arizona
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California
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Connecticut
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Florida
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Idaho
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Illinois
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United States of America
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Louisiana
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United States of America
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Maine
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Maryland
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Michigan
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Missouri
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Nebraska
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New Jersey
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South Carolina
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Tennessee
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Texas
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Washington
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Argentina
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Buenos Aires
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Belgium
State/province [20] 0 0
Antwerp
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Belgium
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Brugge
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Belgium
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Bruxelles
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Belgium
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Leuven
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Canada
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Hamilton
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Canada
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Montreal
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Canada
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Toronto
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China
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Beijing
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China
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Hangzhou
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France
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Avignon
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France
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Bayonne
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France
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Brest
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France
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Lille
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France
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Nantes
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France
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Paris
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France
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Vandœuvre-lès-Nancy
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Germany
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Aachen
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Germany
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Berlin
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Germany
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Bonn
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Germany
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Freiburg
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Germany
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Hamburg
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Germany
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Jena
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Germany
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Magdeburg
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Germany
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Mannheim
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Germany
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Minden
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Germany
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Munchen
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Germany
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Ulm
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Hungary
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Budapest
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Hungary
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Kecskemet
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Hungary
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Szeged
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Hungary
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Szombathely
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Bari
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Italy
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Bergamo
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Italy
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Bologna
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Italy
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Firenze
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Italy
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Milano
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Italy
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Napoli
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Italy
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Orbassano
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Italy
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Pavia
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Italy
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Reggio Calabria
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Italy
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Roma
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Italy
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Varese
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Italy
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Vicenza
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Japan
State/province [63] 0 0
Chiba
Country [64] 0 0
Japan
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Chuo-city Yamanashi
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Japan
State/province [65] 0 0
Maebashi
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Japan
State/province [66] 0 0
Nagoya-city Aichi
Country [67] 0 0
Japan
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Osaka
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Japan
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Tokyo
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Korea, Republic of
State/province [69] 0 0
Seoul
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Netherlands
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Enschede
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Netherlands
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Rotterdam
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Russian Federation
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Moscow
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Russian Federation
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St. Petersburg
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Spain
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Barcelona
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Spain
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Coruña
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Spain
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Las Palmas de Gran Canaria
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Spain
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Madrid
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Spain
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Majadahonda
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Spain
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Malaga
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Spain
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Pamplona
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Spain
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Salamanca
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Spain
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Valencia
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Thailand
State/province [83] 0 0
Bangkok
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Turkey
State/province [84] 0 0
Ankara
Country [85] 0 0
Turkey
State/province [85] 0 0
Istanbul
Country [86] 0 0
Turkey
State/province [86] 0 0
Izmir
Country [87] 0 0
United Kingdom
State/province [87] 0 0
Bournemouth
Country [88] 0 0
United Kingdom
State/province [88] 0 0
Cardiff
Country [89] 0 0
United Kingdom
State/province [89] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Incyte Corporation
Address
Country
Other collaborator category [1] 0 0
Commercial sector/industry
Name [1] 0 0
Novartis Pharmaceuticals
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT01243944
Trial related presentations / publications
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.
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Srdan Verstovsek, MD,PhD
Address 0 0
M.D. Anderson Cancer Center
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01243944