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

November 17, 2010
April 8, 2015
October 2010
January 2014   (final data collection date for primary outcome measure)
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).
Proportion of subjects achieving a response at Week 32. 'Response' is defined as having achieved both: (1) the absence of protocol-defined phlebotomy eligibility and (2) a ≥ 35% reduction from baseline in spleen volume as determined by imaging [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01243944 on ClinicalTrials.gov Archive Site
  • 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.
  • Proportion of subjects achieving complete hematologic remission at Week 32. [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
  • Proportion of all randomized subjects who both achieve the Week 32 primary response endpoint and maintain response for ≥ 48 weeks from the time that response was initially documented. [ Time Frame: At least 80 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
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)
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 subjects with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea (HU).

Not Provided
Interventional
Phase 3
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Polycythemia Vera
  • 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 (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
  • 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
    Intervention: Drug: ruxolitinib tablets
  • 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.
    Intervention: Other: Best Available Therapy (BAT)
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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
222
December 2018
January 2014   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States,   Argentina,   Australia,   Belgium,   Canada,   China,   France,   Germany,   Hungary,   Italy,   Japan,   Korea, Republic of,   Netherlands,   Russian Federation,   Spain,   Thailand,   Turkey,   United Kingdom
 
NCT01243944
CINC424B2301
Not Provided
Incyte Corporation
Incyte Corporation
Novartis Pharmaceuticals
Study Director: Srdan Verstovsek, MD,PhD M.D. Anderson Cancer Center
Study Director: Mark Jones, MD Incyte Corporation
Incyte Corporation
April 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP