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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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ClinicalTrials.gov Identifier: NCT01243944
Recruitment Status : Active, not recruiting
First Posted : November 19, 2010
Results First Posted : March 6, 2015
Last Update Posted : June 14, 2017
Sponsor:
Collaborator:
Information provided by (Responsible Party):

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 subjects with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea (HU).

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

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 222 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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)
Study Start Date : October 2010
Primary Completion Date : January 2014
Estimated Study Completion Date : December 2018


Arms and Interventions

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
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


Outcome Measures

Primary Outcome Measures :
  1. The Percentage of Subjects 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).


Secondary Outcome Measures :
  1. The Percentage of Subjects Achieving a Durable Primary Response at Week 48 [ Time Frame: 48 Weeks ]
    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.

  2. The Percentage of Subjects Achieving Complete Hematological Remission at Week 32 [ Time Frame: 32 Weeks ]
    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.

  3. The Percentage of Subjects Who Achieved a Durable Complete Hematological Remission at Week 48 [ Time Frame: 48 Weeks ]
    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.

  4. The Percentage of Subjects Who Achieved a Durable Hematocrit Control at Week 48 [ Time Frame: 48 Weeks ]
    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.

  5. The Percentage of Subjects Who Achieved Durable Spleen Volume Reduction at Week 48 [ Time Frame: 48 Weeks ]
    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.

  6. 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 ]

    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.


  7. The Percentage of Subjects Who Achieved Overall Clinicohematologic Response at Week 32 [ Time Frame: 32 Weeks ]
    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.

  8. The Percentage of Subjects 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 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.

  9. 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 ]

    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.



Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01243944


  Show 102 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:
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
First Posted: November 19, 2010    Key Record Dates
Results First Posted: March 6, 2015
Last Update Posted: June 14, 2017
Last Verified: May 2017

Keywords provided by Incyte Corporation:
INCB018424

Additional relevant MeSH terms:
Polycythemia
Polycythemia Vera
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Bone Marrow Diseases
Myeloproliferative Disorders
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