Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT01243944
First received: November 17, 2010
Last updated: September 21, 2016
Last verified: September 2016
  Purpose
This pivotal phase III trial (CINC424B2301) is designed to compare the efficacy and safety of ruxolitinib (INC424) to Best Available Therapy (BAT) in subjects with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea (HU).

Condition Intervention Phase
Polycythemia Vera
Drug: ruxolitinib tablets
Other: Best Available Therapy (BAT)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Incyte Corporation:

Primary Outcome Measures:
  • The Percentage of Subjects Achieving a Primary Response at Week 32 [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
    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 Subjects Achieving a Durable Primary Response at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Durable Primary Response was defined as any subject who achieved the primary outcome measure and who maintained their response up to 48 weeks after randomization.

  • The Percentage of Subjects Achieving Complete Hematological Remission at Week 32 [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
    Complete Hematological Remission at Week 32 was defined as any subject 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 Subjects Who Achieved a Durable Complete Hematological Remission at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Durable Complete Hematological Remission was defined as any subject who achieved Complete Hematological Remission at Week 32 and maintained their response up to 48 weeks after randomization.

  • The Percentage of Subjects Who Achieved a Durable Hematocrit Control at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Durable Hematocrit Control was defined as any subject who achieved phlebotomy eligibility independence from Week 8 to Week 32 and maintained hematocrit control up to 48 weeks after randomization.

  • The Percentage of Subjects Who Achieved Durable Spleen Volume Reduction at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Durable Spleen Volume Reduction was defined as a subject 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 [ Time Frame: Through study completion, analysis was conducted when all patients had completed the Week 80 visit or discontinued the study ] [ Designated as safety issue: No ]

    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 Subjects Who Achieved Overall Clinicohematologic Response at Week 32 [ Time Frame: 32 Weeks ] [ Designated as safety issue: No ]
    Overall Clinicohematologic Response is defined as any subject 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 Subjects Achieving a Durable Complete or Partial Clinicohematologic Response at Week 48 [ Time Frame: 48 Weeks ] [ Designated as safety issue: No ]
    Durable Complete or Partial Clinicohematologic Response was defined as any subject 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 [ Time Frame: Through study completion, analysis was conducted when all patients had completed the Week 80 visit or discontinued the study ] [ Designated as safety issue: No ]

    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.



Enrollment: 222
Study Start Date: October 2010
Estimated Study Completion Date: December 2018
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Best Available Therapy
Best Available Therapy (BAT) will be selected by the Investigator for each subject. 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 subject. 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:
  • BAT could include:
  • Hydroxyurea
  • IFN/PEG-IFN
  • Pipobroman
  • Anagrelide
  • Lenalidomide
  • Pomalidomide
  • Observation only

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects diagnosed with PV for at least 24 weeks prior to screening according to the 2008 World Health Organization criteria
  • Subjects resistant to or intolerant of hydroxyurea
  • Subjects with a phlebotomy requirement
  • Subjects with splenomegaly (palpable or non-palpable) and a spleen volume, as measured by MRI (or CT in applicable subjects), of greater than or equal to 450 cubic centimeters
  • Subjects with an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2

Exclusion Criteria:

  • Women who are pregnant or nursing
  • Subjects with inadequate liver or renal function
  • Subjects with significant bacterial, fungal, parasitic, or viral infection requiring treatment
  • Subjects with an active malignancy within the past 5 years, excluding specific skin cancers
  • Subjects with known active hepatitis or HIV positivity
  • Subjects who have previously received treatment with a JAK inhibitor
  • Subjects being treated with any investigational agent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01243944

  Hide Study Locations
Locations
United States, Alabama
Birmingham, Alabama, United States
United States, Arizona
Scottsdale, Arizona, United States
United States, California
Pomona, California, United States
Sacramento, California, United States
San Diego, California, United States
United States, Connecticut
Bridgeport, Connecticut, United States
New Haven, Connecticut, United States
United States, Florida
Boynton Beach, Florida, United States
Fort Myers, Florida, United States
Jacksonville, Florida, United States
Winter Park, Florida, United States
United States, Idaho
Boise, Idaho, United States
United States, Illinois
Chicago, Illinois, United States
United States, Louisiana
Lafayette, Louisiana, United States
United States, Maine
Scarborough, Maine, United States
United States, Maryland
Baltimore, Maryland, United States
Columbia, Maryland, United States
United States, Michigan
Southfield, Michigan, United States
United States, Missouri
Jefferson City, Missouri, United States
Saint Louis, Missouri, United States
United States, Nebraska
Omaha, Nebraska, United States
United States, New Jersey
Morristown, New Jersey, United States
Somerville, New Jersey, United States
United States, South Carolina
Charleston, South Carolina, United States
Greenville, South Carolina, United States
United States, Tennessee
Nashville, Tennessee, United States
United States, Texas
Houston, Texas, United States
United States, Washington
Seattle, Washington, United States
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
Vandeuvre Les 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-city Gunma, 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
La Coruna Galicia, Spain
Las Palmas de Gran Canaria, Spain
Madrid, Spain
Majadanonda, Spain
Malaga, Spain
Pamplona Navarra, Spain
Salamanca Leon, Spain
Valencia, Spain
Thailand
Bangkok, Thailand
Turkey
Ankara, Turkey
Istanbul, Turkey
Izmir, Turkey
United Kingdom
Bournmouth, United Kingdom
Cardiff, United Kingdom
London, United Kingdom
Sponsors and Collaborators
Incyte Corporation
Novartis Pharmaceuticals
Investigators
Study Director: Srdan Verstovsek, MD,PhD M.D. Anderson Cancer Center
Study Director: Mark Jones, MD Incyte Corporation
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT01243944     History of Changes
Other Study ID Numbers: CINC424B2301 
Study First Received: November 17, 2010
Results First Received: December 22, 2014
Last Updated: September 21, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Incyte Corporation:
INCB018424

Additional relevant MeSH terms:
Polycythemia
Polycythemia Vera
Hematologic Diseases
Myeloproliferative Disorders
Bone Marrow Diseases
Lenalidomide
Pomalidomide
Hydroxyurea
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on December 02, 2016