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)

February 8, 2019 updated by: Incyte Corporation

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)

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

222

Phase

  • Phase 3

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
  • Australia
      • Brisbane, Australia
      • Parkville, Australia
      • Tweed Heads, Australia
  • Belgium
      • Antwerp, Belgium
      • Brugge, Belgium
      • Bruxelles, Belgium
      • Leuven, Belgium
  • Canada
      • Hamilton, Canada
      • Montreal, Canada
      • Toronto, Canada
  • China
      • Beijing, China
      • Hangzhou, China
  • France
      • Avignon, France
      • Bayonne, France
      • Brest, France
      • Lille, France
      • Nantes, France
      • Paris, France
      • Vandœuvre-lès-Nancy, France
  • Germany
      • Aachen, Germany
      • Berlin, Germany
      • Bonn, Germany
      • Freiburg, Germany
      • Hamburg, Germany
      • Jena, Germany
      • Magdeburg, Germany
      • Mannheim, Germany
      • Minden, Germany
      • Munchen, Germany
      • Ulm, Germany
  • Hungary
      • Budapest, Hungary
      • Kecskemet, Hungary
      • Szeged, Hungary
      • Szombathely, Hungary
  • Italy
      • Bari, Italy
      • Bergamo, Italy
      • Bologna, Italy
      • Firenze, Italy
      • Milano, Italy
      • Napoli, Italy
      • Orbassano, Italy
      • Pavia, Italy
      • Reggio Calabria, Italy
      • Roma, Italy
      • Varese, Italy
      • Vicenza, Italy
  • Japan
      • Chiba, Japan
      • Chuo-city Yamanashi, Japan
      • Maebashi, Japan
      • Nagoya-city Aichi, Japan
      • Osaka, Japan
      • Tokyo, Japan
  • Korea, Republic of
      • Seoul, Korea, Republic of
  • Netherlands
      • Enschede, Netherlands
      • Rotterdam, Netherlands
  • Russian Federation
      • Moscow, Russian Federation
      • St. Petersburg, Russian Federation
  • Spain
      • Barcelona, Spain
      • Coruña, Spain
      • Las Palmas de Gran Canaria, Spain
      • Madrid, Spain
      • Majadahonda, Spain
      • Malaga, Spain
      • Pamplona, Spain
      • Salamanca, Spain
      • Valencia, Spain
  • Thailand
      • Bangkok, Thailand
  • Turkey
      • Ankara, Turkey
      • Istanbul, Turkey
      • Izmir, Turkey
  • United Kingdom
      • Bournemouth, United Kingdom
      • Cardiff, United Kingdom
      • London, United Kingdom
  • United States
    • Alabama
      • Birmingham, Alabama, United States
    • Arizona
      • Scottsdale, Arizona, United States
    • California
      • Pomona, California, United States
      • Sacramento, California, United States
      • San Diego, California, United States
    • Connecticut
      • Bridgeport, Connecticut, United States
      • New Haven, Connecticut, United States
    • Florida
      • Boynton Beach, Florida, United States
      • Fort Myers, Florida, United States
      • Jacksonville, Florida, United States
      • Winter Park, Florida, United States
    • Idaho
      • Boise, Idaho, United States
    • Illinois
      • Chicago, Illinois, United States
    • Louisiana
      • Lafayette, Louisiana, United States
    • Maine
      • Scarborough, Maine, United States
    • Maryland
      • Baltimore, Maryland, United States
      • Columbia, Maryland, United States
    • Michigan
      • Southfield, Michigan, United States
    • Missouri
      • Jefferson City, Missouri, United States
      • Saint Louis, Missouri, United States
    • Nebraska
      • Omaha, Nebraska, United States
    • New Jersey
      • Morristown, New Jersey, United States
      • Somerville, New Jersey, United States
    • South Carolina
      • Charleston, South Carolina, United States
      • Greenville, South Carolina, United States
    • Tennessee
      • Nashville, Tennessee, United States
    • Texas
      • Houston, Texas, United States
    • Washington
      • Seattle, Washington, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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
Drug: 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: 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.
Other: 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.
Other Names:
  • Lenalidomide
  • Hydroxyurea
  • Pomalidomide
  • BAT could include:
  • IFN/PEG-IFN
  • Pipobroman
  • Anagrelide
  • Observation only

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Percentage of Participants Achieving a Primary Response at Week 32
Time Frame: 32 Weeks
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Percentage of Participants Achieving a Durable Primary Response at Week 48
Time Frame: 48 Weeks
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.
48 Weeks
The Percentage of Participants Achieving Complete Hematological Remission at Week 32
Time Frame: 32 Weeks
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.
32 Weeks
The Percentage of Participants Who Achieved a Durable Complete Hematological Remission at Week 48
Time Frame: 48 Weeks
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.
48 Weeks
The Percentage of Participants Who Achieved a Durable Hematocrit Control at Week 48
Time Frame: 48 Weeks
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.
48 Weeks
The Percentage of Participants Who Achieved Durable Spleen Volume Reduction at Week 48
Time Frame: 48 Weeks
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.
48 Weeks
Estimated Duration of the Primary Response
Time Frame: Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study

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.
Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study
The Percentage of Participants Who Achieved Overall Clinicohematologic Response at Week 32
Time Frame: 32 Weeks
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.
32 Weeks
The Percentage of Participants Achieving a Durable Complete or Partial Clinicohematologic Response at Week 48
Time Frame: 48 Weeks
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.
48 Weeks
Estimated Duration of the Complete Hematological Remission
Time Frame: Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study

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.
Through study completion, analysis was conducted when all participants had completed the Week 80 visit or discontinued the study
Duration of the Absence of Phlebotomy Eligibility
Time Frame: 256 Weeks
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.
256 Weeks
Duration of Reduction in Spleen Volume
Time Frame: 256 Weeks
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.
256 Weeks
Duration of The Overall Clinicohematologic Response
Time Frame: 256 Weeks
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.
256 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Incyte Corporation

Collaborators

Novartis Pharmaceuticals

Investigators

  • Study Director: Srdan Verstovsek, MD,PhD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

October 27, 2010

Primary Completion (ACTUAL)

January 15, 2014

Study Completion (ACTUAL)

February 9, 2018

Study Registration Dates

First Submitted

November 17, 2010

First Submitted That Met QC Criteria

November 18, 2010

First Posted (ESTIMATE)

November 19, 2010

Study Record Updates

Last Update Posted (ACTUAL)

March 6, 2019

Last Update Submitted That Met QC Criteria

February 8, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CINC424B2301

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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