Back to resultsStudy 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)
Primary Purpose
Polycythemia Vera
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
ruxolitinib tablets
Best Available Therapy (BAT)
Sponsored by
About this trial
This is an interventional treatment trial for Polycythemia Vera focused on measuring INCB018424
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
ruxolitinib tablets
Best Available Therapy
Arm Description
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
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.
Outcomes
Primary Outcome Measures
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).
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Full Information
NCT ID
NCT01243944
First Posted
November 17, 2010
Last Updated
February 8, 2019
Sponsor
Incyte Corporation
Collaborators
Novartis Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT01243944
Brief 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)
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
2. Study Status
Record Verification Date
February 2019
Overall Recruitment Status
Completed
Study Start Date
October 27, 2010 (Actual)
Primary Completion Date
January 15, 2014 (Actual)
Study Completion Date
February 9, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation
Collaborators
Novartis Pharmaceuticals
4. Oversight
5. Study Description
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).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycythemia Vera
Keywords
INCB018424
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
222 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ruxolitinib tablets
Arm Type
Experimental
Arm Description
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
Arm Title
Best Available Therapy
Arm Type
Other
Arm Description
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
Drug
Intervention Name(s)
ruxolitinib tablets
Intervention Description
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
Other
Intervention Name(s)
Best Available Therapy (BAT)
Other Intervention Name(s)
BAT could include:, Hydroxyurea, IFN/PEG-IFN, Pipobroman, Anagrelide, Lenalidomide, Pomalidomide, Observation only
Intervention Description
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.
Primary Outcome Measure Information:
Title
The Percentage of Participants Achieving a Primary Response at Week 32
Description
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).
Time Frame
32 Weeks
Secondary Outcome Measure Information:
Title
The Percentage of Participants Achieving a Durable Primary Response at Week 48
Description
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.
Time Frame
48 Weeks
Title
The Percentage of Participants Achieving Complete Hematological Remission at Week 32
Description
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.
Time Frame
32 Weeks
Title
The Percentage of Participants Who Achieved a Durable Complete Hematological Remission at Week 48
Description
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.
Time Frame
48 Weeks
Title
The Percentage of Participants Who Achieved a Durable Hematocrit Control at Week 48
Description
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.
Time Frame
48 Weeks
Title
The Percentage of Participants Who Achieved Durable Spleen Volume Reduction at Week 48
Description
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.
Time Frame
48 Weeks
Title
Estimated Duration of the Primary Response
Description
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.
Time Frame
Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study
Title
The Percentage of Participants Who Achieved Overall Clinicohematologic Response at Week 32
Description
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.
Time Frame
32 Weeks
Title
The Percentage of Participants Achieving a Durable Complete or Partial Clinicohematologic Response at Week 48
Description
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.
Time Frame
48 Weeks
Title
Estimated Duration of the Complete Hematological Remission
Description
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.
Time Frame
Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study
Title
Duration of the Absence of Phlebotomy Eligibility
Description
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.
Time Frame
256 Weeks
Title
Duration of Reduction in Spleen Volume
Description
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.
Time Frame
256 Weeks
Title
Duration of The Overall Clinicohematologic Response
Description
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.
Time Frame
256 Weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Srdan Verstovsek, MD,PhD
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Study Director
First Name & Middle Initial & Last Name & Degree
Mark Jones, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
City
Birmingham
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Alabama
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United States
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Scottsdale
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Arizona
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Pomona
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Sacramento
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Boise
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Columbia
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Parkville
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Tweed Heads
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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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Hamilton
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Montreal
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Toronto
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Beijing
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China
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Hangzhou
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China
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Avignon
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Bayonne
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Brest
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Lille
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Nantes
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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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Germany
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Germany
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Germany
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Germany
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Germany
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Germany
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Ulm
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Szeged
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Hungary
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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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Italy
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Chiba
Country
Japan
City
Chuo-city Yamanashi
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Japan
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Maebashi
Country
Japan
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Nagoya-city Aichi
Country
Japan
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Osaka
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Japan
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Tokyo
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Japan
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Seoul
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Korea, Republic of
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Enschede
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Netherlands
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Rotterdam
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Netherlands
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Moscow
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Russian Federation
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St. Petersburg
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Russian Federation
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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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Spain
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Bangkok
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Thailand
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Ankara
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Turkey
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Istanbul
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Turkey
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Izmir
Country
Turkey
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Bournemouth
Country
United Kingdom
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Cardiff
Country
United Kingdom
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London
Country
United Kingdom
12. IPD Sharing Statement
Citations:
PubMed Identifier
31982039
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.
Results Reference
derived
PubMed Identifier
29396713
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.
Results Reference
derived
PubMed Identifier
28193568
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.
Results Reference
derived
PubMed Identifier
27102499
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.
Results Reference
derived
PubMed Identifier
25629741
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.
Results Reference
derived
Learn more about this trial
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)
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