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:
Incyte Corporation
Collaborator:
Novartis Pharmaceuticals
Information provided by (Responsible Party):
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT01243944
First received: November 17, 2010
Last updated: October 14, 2015
Last verified: October 2015
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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:
Genetics Home Reference related topics:
polycythemia vera
Genetic and Rare Diseases Information Center resources:
Polycythemia Vera
Chronic Myeloproliferative Disorders
U.S. FDA Resources
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:
|
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 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
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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 129 Study Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01243944
Show 129 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 |
| Study First Received: | November 17, 2010 |
| Results First Received: | December 22, 2014 |
| Last Updated: | October 14, 2015 |
| 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 September 27, 2016