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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/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 - 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).
Timepoint [1] 0 0
32 Weeks
Secondary outcome [1] 0 0
The Percentage of Participants Achieving a Durable Primary Response at Week 48 - Durable Primary Response was defined as any participant who achieved the primary outcome measure and who maintained their response up to 48 weeks after randomization.
Timepoint [1] 0 0
48 Weeks
Secondary outcome [2] 0 0
The Percentage of Participants Achieving Complete Hematological Remission at Week 32 - Complete Hematological Remission at Week 32 was defined as any participant who achieved hematocrit control with a platelet count less than or equal to 400 X 10^9/L and a white blood cell count less than or equal to 10 X 10^9/L.
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 - Durable Complete Hematological Remission was defined as any participant who achieved Complete Hematological Remission at Week 32 and maintained their response up to 48 weeks after randomization.
Timepoint [3] 0 0
48 Weeks
Secondary outcome [4] 0 0
The Percentage of Participants Who Achieved a Durable Hematocrit Control at Week 48 - Durable Hematocrit Control was defined as any participant who achieved phlebotomy eligibility independence from Week 8 to Week 32 and maintained hematocrit control up to 48 weeks after randomization.
Timepoint [4] 0 0
48 Weeks
Secondary outcome [5] 0 0
The Percentage of Participants Who Achieved Durable Spleen Volume Reduction at Week 48 - Durable Spleen Volume Reduction was defined as a participant who achieved at least 35% reduction from baseline in spleen volume at Week 32 and maintained that response 48 weeks after randomization.
Timepoint [5] 0 0
48 Weeks
Secondary outcome [6] 0 0
Estimated Duration of the Primary Response - Duration of the primary response is defined as the time from the first occurrence when both components of the primary endpoint are met until the date of the first documented disease progression (end of response).
Kaplan-Meier estimates are provided for duration of 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 - Overall Clinicohematologic Response is defined as any participant who achieved a complete or partial clinicohematologic response per the European LeukemiaNet modified criteria for response in polycythemia vera (PV). A Complete Response (CR) is defined as: hematocrit control, spleen volume reduction at least 35% from baseline, platelet count less than or equal to 400 x 10(9)/L, and white blood cell count less than or equal to 10 x 10(9)/L. A Partial Response (PR) is defined as hematocrit control or response in all 3 of the other criteria.
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 - Durable Complete or Partial Clinicohematologic Response was defined as any participant who achieved complete or partial clinicohematologic response per the European LeukemiaNet modified criteria for response in polycythemia vera at Week 32 and maintained that response 48 weeks after randomization.
Timepoint [8] 0 0
48 Weeks
Secondary outcome [9] 0 0
Estimated Duration of the Complete Hematological Remission - Duration of the complete hematological remission is defined as the time from the first occurrence of complete hematological remission until the date of the first documented progression (end of response).
Kaplan-Meier estimates are provided for duration of 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 - Duration of the absence of phlebotomy eligibility is defined as the time from the first occurrence of absence of phlebotomy eligibility until the date of the first documented progression.
Timepoint [10] 0 0
256 Weeks
Secondary outcome [11] 0 0
Duration of Reduction in Spleen Volume - Duration of spleen volume reduction is defined as the time from the first occurrence of a >=35% reduction from baseline in spleen volume until the date of the first documented progression.
Timepoint [11] 0 0
256 Weeks
Secondary outcome [12] 0 0
Duration of The Overall Clinicohematologic Response - Duration of the overall clinicohematologic response was defined as the time from the first occurrence of complete response (CR) or partial response (PR) until the date of the first documented disease progression.
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
Gender
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
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Connecticut
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Florida
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United States of America
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Idaho
Country [7] 0 0
United States of America
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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
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Michigan
Country [12] 0 0
United States of America
State/province [12] 0 0
Missouri
Country [13] 0 0
United States of America
State/province [13] 0 0
Nebraska
Country [14] 0 0
United States of America
State/province [14] 0 0
New Jersey
Country [15] 0 0
United States of America
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South Carolina
Country [16] 0 0
United States of America
State/province [16] 0 0
Tennessee
Country [17] 0 0
United States of America
State/province [17] 0 0
Texas
Country [18] 0 0
United States of America
State/province [18] 0 0
Washington
Country [19] 0 0
Argentina
State/province [19] 0 0
Buenos Aires
Country [20] 0 0
Belgium
State/province [20] 0 0
Antwerp
Country [21] 0 0
Belgium
State/province [21] 0 0
Brugge
Country [22] 0 0
Belgium
State/province [22] 0 0
Bruxelles
Country [23] 0 0
Belgium
State/province [23] 0 0
Leuven
Country [24] 0 0
Canada
State/province [24] 0 0
Hamilton
Country [25] 0 0
Canada
State/province [25] 0 0
Montreal
Country [26] 0 0
Canada
State/province [26] 0 0
Toronto
Country [27] 0 0
China
State/province [27] 0 0
Beijing
Country [28] 0 0
China
State/province [28] 0 0
Hangzhou
Country [29] 0 0
France
State/province [29] 0 0
Avignon
Country [30] 0 0
France
State/province [30] 0 0
Bayonne
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France
State/province [31] 0 0
Brest
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France
State/province [32] 0 0
Lille
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France
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Nantes
Country [34] 0 0
France
State/province [34] 0 0
Paris
Country [35] 0 0
France
State/province [35] 0 0
VandÅ“uvre-lès-Nancy
Country [36] 0 0
Germany
State/province [36] 0 0
Aachen
Country [37] 0 0
Germany
State/province [37] 0 0
Berlin
Country [38] 0 0
Germany
State/province [38] 0 0
Bonn
Country [39] 0 0
Germany
State/province [39] 0 0
Freiburg
Country [40] 0 0
Germany
State/province [40] 0 0
Hamburg
Country [41] 0 0
Germany
State/province [41] 0 0
Jena
Country [42] 0 0
Germany
State/province [42] 0 0
Magdeburg
Country [43] 0 0
Germany
State/province [43] 0 0
Mannheim
Country [44] 0 0
Germany
State/province [44] 0 0
Minden
Country [45] 0 0
Germany
State/province [45] 0 0
Munchen
Country [46] 0 0
Germany
State/province [46] 0 0
Ulm
Country [47] 0 0
Hungary
State/province [47] 0 0
Budapest
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Hungary
State/province [48] 0 0
Kecskemet
Country [49] 0 0
Hungary
State/province [49] 0 0
Szeged
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Hungary
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Szombathely
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Italy
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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
State/province [57] 0 0
Orbassano
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Italy
State/province [58] 0 0
Pavia
Country [59] 0 0
Italy
State/province [59] 0 0
Reggio Calabria
Country [60] 0 0
Italy
State/province [60] 0 0
Roma
Country [61] 0 0
Italy
State/province [61] 0 0
Varese
Country [62] 0 0
Italy
State/province [62] 0 0
Vicenza
Country [63] 0 0
Japan
State/province [63] 0 0
Chiba
Country [64] 0 0
Japan
State/province [64] 0 0
Chuo-city Yamanashi
Country [65] 0 0
Japan
State/province [65] 0 0
Maebashi
Country [66] 0 0
Japan
State/province [66] 0 0
Nagoya-city Aichi
Country [67] 0 0
Japan
State/province [67] 0 0
Osaka
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Japan
State/province [68] 0 0
Tokyo
Country [69] 0 0
Korea, Republic of
State/province [69] 0 0
Seoul
Country [70] 0 0
Netherlands
State/province [70] 0 0
Enschede
Country [71] 0 0
Netherlands
State/province [71] 0 0
Rotterdam
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Russian Federation
State/province [72] 0 0
Moscow
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Russian Federation
State/province [73] 0 0
St. Petersburg
Country [74] 0 0
Spain
State/province [74] 0 0
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
State/province [81] 0 0
Salamanca
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Spain
State/province [82] 0 0
Valencia
Country [83] 0 0
Thailand
State/province [83] 0 0
Bangkok
Country [84] 0 0
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/show/NCT01243944
Trial related presentations / publications
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
Other publications