Back to resultsPhase 2 Study of Ruxolitinib Versus Anagrelide in Subjects With Essential Thrombocythemia Who Are Resistant to or Intolerant of Hydroxyurea (RESET-272)
Primary Purpose
MPN (Myeloproliferative Neoplasms)
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Ruxolitinib
Anagrelide
Placebo
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for MPN (Myeloproliferative Neoplasms) focused on measuring Essential thrombocythemia, hydroxyurea-resistant, hydroxyurea-intolerant, ruxolitinib, anagrelide
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of essential thrombocythemia according to revised World Health Organization (WHO) 2016 criteria.
Resistant to or intolerant of hydroxyurea, that is, fulfilling at least 1 of the following criteria:
- Platelet count > 600 × 10^9/L after 3 months of at least 2 g/day of hydroxyurea (2.5 g/day in subjects with a body weight over 80 kg) OR at the subject's maximally tolerated dose if that dose is < 2 g/day.
- Platelet count > 400 × 10^9/L and WBC count < 2.5 × 10^9/L or hemoglobin < 10 g/dL at any dose of hydroxyurea.
- Presence of leg ulcers or other unacceptable mucocutaneous manifestations at any dose of hydroxyurea.
- Hydroxyurea-related fever.
- Platelet count ≥ 650 × 10^9/L at screening.
- WBC ≥ 11.0 × 10^9/L at screening.
Exclusion Criteria:
Subjects previously treated with anagrelide or Hydroxyurea (HU).
- Prior anagrelide use is allowed provided the reason for discontinuation is not AE-related and anagrelide is stopped at least 28 days before the start of study medications (ie, Day 1).
- Treatment with HU can be stopped at any time once one of the inclusion criteria for HU refractoriness or resistance have been met, and up to the day before the first dose of study treatment (ie, Day 1).
Inadequate liver function at screening and Day 1 (before drug administration) as demonstrated by:
- Total bilirubin > 1.5 × upper limit of normal (ULN)
- Aspartate aminotransferase or alanine aminotransferase > 1.5 × ULN
- Hepatocellular disease (eg, cirrhosis)
- Inadequate renal function at screening as demonstrated by creatinine clearance < 40 mL/min calculated by Cockcroft-Gault equation.
Sites / Locations
- Mayo Clinic
- Pacific Shores Medical Group
- University of Southern California
- Ventura County Hematology-Oncology Specialists
- Compassionate Cancer Care Medical Group
- Innovative Clinical Research Institute
- Bond Clinic, PA
- Tift Regional
- Edward Cancer Center
- North Shore Cancer Research Association-Skokie
- Southern Illinois University
- Clinical Trials of SWLA LLC
- St. Agnes Hospital
- Washington University School of Medicine
- Summit Medical Group
- Montefiore Medical Center
- Columbia Weill Cornell Cancer Centers - Herbert Irving Comprehensive Cancer Center (HICCC)
- Waverly Hem Onc
- Vidant Medical Center
- Gabrail Cancer Center- Canton Facility
- INTEGRIS Southwest Medical Center
- INTEGRIS Cancer Institute Proton Campus
- Kaiser Permanente Northwest
- Geisinger - Knapper Clinic
- Prairie Lakes Health Care System Inc.
- Renovatio Clinical
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Group A : Ruxolitinib and anagrelide placebo
Group B : Anagrelide and Ruxolitinib PLacebo
Arm Description
Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.
Anagrelide or placebo will be administered orally twice a day at a starting dose of 1 mg. Use of anagrelide will be consistent with approved prescribing information.
Outcomes
Primary Outcome Measures
Proportion of Subjects Who Achieve Platelet and White Blood Cell (WBC) Control
Defined as proportion of subjects who achieve a simultaneous reduction of platelet counts to < 600 × 10^9/L with a reduction of WBC counts to < 10 × 10^9/L for at least 80% of biweekly measurements for a consecutive 12-week period between Weeks 32 and 52.
Secondary Outcome Measures
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Proportion of Subjects Who Achieve Complete Remission or Partial Remission
Defined as proportion of subjects who achieve CR or PR at Week 32 based on European LeukemiaNet (ELN) 2013 response criteria. Per ELN criteria: Complete Remission: durable resolution of disease related signs and symptoms, durable blood count normalization, absence of hemorrhagic or thrombotic events, absence of signs of progressive disease and bone marrow histological remission including disappearance of megakaryocyte hyperplasia and absence of reticulin fibrosis >Grade 1.
Partial remission: durable resolution of disease related signs and symptoms, durable blood count normalization, absence of hemorrhagic or thrombotic events, absence of signs of progressive disease, persistance of megakaryocyte hyperplasia.
No response: any response that does not satisfy partial remission. Progressive Disease: transformation in PET-MF, MDS or acute leukemia.
Time to Treatment Discontinuation
Defined as the time when treatment is discontinued
Duration of Response
Defined as measurement of response from the onset of response to the loss of response for responders.
Proportion of Subjects Who Achieve Reduction of Platelet Counts to < 600 × 10^9/L
Defined as Proportion of subjects who achieve reduction of platelet counts to < 600 × 10^9/L for at least 80% of biweekly measurements for a consecutive 12-week period between Weeks 32 and 52.
Proportion of Subjects Who Achieve a Reduction of WBC Counts to < 10 × 109/L
Defined as Proportion of subjects who achieve a reduction of WBC counts to < 10 × 109/L for at least 80% of biweekly measurements for a consecutive 12-week period between Weeks 32 and 52.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03123588
Brief Title
Phase 2 Study of Ruxolitinib Versus Anagrelide in Subjects With Essential Thrombocythemia Who Are Resistant to or Intolerant of Hydroxyurea (RESET-272)
Official Title
A Double-Blind, Double-Dummy Phase 2 Randomized Study to Evaluate the Efficacy and Safety of Ruxolitinib Versus Anagrelide in Subjects With Essential Thrombocythemia Who Are Resistant to or Intolerant of Hydroxyurea (RESET-272)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Terminated
Why Stopped
Enrollment issues
Study Start Date
November 14, 2017 (Actual)
Primary Completion Date
August 3, 2020 (Actual)
Study Completion Date
August 3, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Incyte Corporation
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of ruxolitinib versus anagrelide in subjects with essential thrombocythemia who are resistant to or intolerant of hydroxyurea.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
MPN (Myeloproliferative Neoplasms)
Keywords
Essential thrombocythemia, hydroxyurea-resistant, hydroxyurea-intolerant, ruxolitinib, anagrelide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
12 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Group A : Ruxolitinib and anagrelide placebo
Arm Type
Experimental
Arm Description
Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.
Arm Title
Group B : Anagrelide and Ruxolitinib PLacebo
Arm Type
Active Comparator
Arm Description
Anagrelide or placebo will be administered orally twice a day at a starting dose of 1 mg. Use of anagrelide will be consistent with approved prescribing information.
Intervention Type
Drug
Intervention Name(s)
Ruxolitinib
Other Intervention Name(s)
Jakafi, INCB018424
Intervention Description
Ruxolitinib administered orally twice daily (BID) at the protocol-defined starting dose.
Intervention Type
Drug
Intervention Name(s)
Anagrelide
Intervention Description
Anagrelide administered orally at a starting dose of 1 mg BID.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Anagrelide-placebo administered orally BID
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Ruxolitinib-placebo administered orally BID.
Primary Outcome Measure Information:
Title
Proportion of Subjects Who Achieve Platelet and White Blood Cell (WBC) Control
Description
Defined as proportion of subjects who achieve a simultaneous reduction of platelet counts to < 600 × 10^9/L with a reduction of WBC counts to < 10 × 10^9/L for at least 80% of biweekly measurements for a consecutive 12-week period between Weeks 32 and 52.
Time Frame
52 weeks
Secondary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Description
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Time Frame
Baseline through the end of randomized period -up to 14 months per participant
Title
Proportion of Subjects Who Achieve Complete Remission or Partial Remission
Description
Defined as proportion of subjects who achieve CR or PR at Week 32 based on European LeukemiaNet (ELN) 2013 response criteria. Per ELN criteria: Complete Remission: durable resolution of disease related signs and symptoms, durable blood count normalization, absence of hemorrhagic or thrombotic events, absence of signs of progressive disease and bone marrow histological remission including disappearance of megakaryocyte hyperplasia and absence of reticulin fibrosis >Grade 1.
Partial remission: durable resolution of disease related signs and symptoms, durable blood count normalization, absence of hemorrhagic or thrombotic events, absence of signs of progressive disease, persistance of megakaryocyte hyperplasia.
No response: any response that does not satisfy partial remission. Progressive Disease: transformation in PET-MF, MDS or acute leukemia.
Time Frame
32 weeks
Title
Time to Treatment Discontinuation
Description
Defined as the time when treatment is discontinued
Time Frame
98 weeks
Title
Duration of Response
Description
Defined as measurement of response from the onset of response to the loss of response for responders.
Time Frame
142 weeks
Title
Proportion of Subjects Who Achieve Reduction of Platelet Counts to < 600 × 10^9/L
Description
Defined as Proportion of subjects who achieve reduction of platelet counts to < 600 × 10^9/L for at least 80% of biweekly measurements for a consecutive 12-week period between Weeks 32 and 52.
Time Frame
Between 32 and 52 weeks
Title
Proportion of Subjects Who Achieve a Reduction of WBC Counts to < 10 × 109/L
Description
Defined as Proportion of subjects who achieve a reduction of WBC counts to < 10 × 109/L for at least 80% of biweekly measurements for a consecutive 12-week period between Weeks 32 and 52.
Time Frame
52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of essential thrombocythemia according to revised World Health Organization (WHO) 2016 criteria.
Resistant to or intolerant of hydroxyurea, that is, fulfilling at least 1 of the following criteria:
Platelet count > 600 × 10^9/L after 3 months of at least 2 g/day of hydroxyurea (2.5 g/day in subjects with a body weight over 80 kg) OR at the subject's maximally tolerated dose if that dose is < 2 g/day.
Platelet count > 400 × 10^9/L and WBC count < 2.5 × 10^9/L or hemoglobin < 10 g/dL at any dose of hydroxyurea.
Presence of leg ulcers or other unacceptable mucocutaneous manifestations at any dose of hydroxyurea.
Hydroxyurea-related fever.
Platelet count ≥ 650 × 10^9/L at screening.
WBC ≥ 11.0 × 10^9/L at screening.
Exclusion Criteria:
Subjects previously treated with anagrelide or Hydroxyurea (HU).
Prior anagrelide use is allowed provided the reason for discontinuation is not AE-related and anagrelide is stopped at least 28 days before the start of study medications (ie, Day 1).
Treatment with HU can be stopped at any time once one of the inclusion criteria for HU refractoriness or resistance have been met, and up to the day before the first dose of study treatment (ie, Day 1).
Inadequate liver function at screening and Day 1 (before drug administration) as demonstrated by:
Total bilirubin > 1.5 × upper limit of normal (ULN)
Aspartate aminotransferase or alanine aminotransferase > 1.5 × ULN
Hepatocellular disease (eg, cirrhosis)
Inadequate renal function at screening as demonstrated by creatinine clearance < 40 mL/min calculated by Cockcroft-Gault equation.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Albert Assad, MD
Organizational Affiliation
Incyte Corporation
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Pacific Shores Medical Group
City
Long Beach
State/Province
California
ZIP/Postal Code
90813
Country
United States
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Ventura County Hematology-Oncology Specialists
City
Oxnard
State/Province
California
ZIP/Postal Code
93030
Country
United States
Facility Name
Compassionate Cancer Care Medical Group
City
Riverside
State/Province
California
ZIP/Postal Code
92501
Country
United States
Facility Name
Innovative Clinical Research Institute
City
Whittier
State/Province
California
ZIP/Postal Code
90603
Country
United States
Facility Name
Bond Clinic, PA
City
Winter Haven
State/Province
Florida
ZIP/Postal Code
33880
Country
United States
Facility Name
Tift Regional
City
Tifton
State/Province
Georgia
ZIP/Postal Code
31794
Country
United States
Facility Name
Edward Cancer Center
City
Naperville
State/Province
Illinois
ZIP/Postal Code
60540
Country
United States
Facility Name
North Shore Cancer Research Association-Skokie
City
Skokie
State/Province
Illinois
ZIP/Postal Code
60076
Country
United States
Facility Name
Southern Illinois University
City
Springfield
State/Province
Illinois
ZIP/Postal Code
62702
Country
United States
Facility Name
Clinical Trials of SWLA LLC
City
Lake Charles
State/Province
Louisiana
ZIP/Postal Code
70601
Country
United States
Facility Name
St. Agnes Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21229
Country
United States
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
Facility Name
Summit Medical Group
City
Morristown
State/Province
New Jersey
ZIP/Postal Code
07960
Country
United States
Facility Name
Montefiore Medical Center
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Columbia Weill Cornell Cancer Centers - Herbert Irving Comprehensive Cancer Center (HICCC)
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
Waverly Hem Onc
City
Cary
State/Province
North Carolina
ZIP/Postal Code
27518
Country
United States
Facility Name
Vidant Medical Center
City
Greenville
State/Province
North Carolina
ZIP/Postal Code
27858
Country
United States
Facility Name
Gabrail Cancer Center- Canton Facility
City
Canton
State/Province
Ohio
ZIP/Postal Code
44718
Country
United States
Facility Name
INTEGRIS Southwest Medical Center
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73109
Country
United States
Facility Name
INTEGRIS Cancer Institute Proton Campus
City
Oklahoma City
State/Province
Oklahoma
ZIP/Postal Code
73142
Country
United States
Facility Name
Kaiser Permanente Northwest
City
Portland
State/Province
Oregon
ZIP/Postal Code
97227
Country
United States
Facility Name
Geisinger - Knapper Clinic
City
Danville
State/Province
Pennsylvania
ZIP/Postal Code
17822
Country
United States
Facility Name
Prairie Lakes Health Care System Inc.
City
Watertown
State/Province
South Dakota
ZIP/Postal Code
57201
Country
United States
Facility Name
Renovatio Clinical
City
The Woodlands
State/Province
Texas
ZIP/Postal Code
77401
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Phase 2 Study of Ruxolitinib Versus Anagrelide in Subjects With Essential Thrombocythemia Who Are Resistant to or Intolerant of Hydroxyurea (RESET-272)
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