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: April 8, 2015
Last verified: April 2015
  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 ] [ Designated as safety issue: No ]
    Duration of 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.

  • 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 Overall Clinicohematologic Response [ Time Frame: Through study completion ] [ Designated as safety issue: No ]
    Duration of the clinicohematologic overall response (Complete Response (CR) or Partial Response (PR)) is defined as the time from the first occurrence of CR or PR until the date of the first documented disease progression.


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
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 a palpable splenomegaly 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

  Show 161 Study Locations
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:
No publications provided by Incyte Corporation

Additional 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: April 8, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Incyte Corporation:
INCB018424

Additional relevant MeSH terms:
Polycythemia
Polycythemia Vera
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Hydroxyurea
Antineoplastic Agents
Antisickling Agents
Enzyme Inhibitors
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Nucleic Acid Synthesis Inhibitors
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 29, 2015