Phase 2 Study of Ruxolitinib Versus Anagrelide in Subjects With Essential Thrombocythemia Who Are Resistant to or Intolerant of Hydroxyurea (RESET-272)
- Conditions
- MPN (Myeloproliferative Neoplasms)
- Interventions
- Registration Number
- NCT03123588
- Lead Sponsor
- Incyte Corporation
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 12
-
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.
-
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A : Ruxolitinib and anagrelide placebo Ruxolitinib Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg. Group A : Ruxolitinib and anagrelide placebo Placebo Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg. Group B : Anagrelide and Ruxolitinib PLacebo Placebo 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. Group B : Anagrelide and Ruxolitinib PLacebo Anagrelide 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.
- Primary Outcome Measures
Name Time Method Proportion of Subjects Who Achieve Platelet and White Blood Cell (WBC) Control 52 weeks 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
Name Time Method Number of Participants With Treatment Emergent Adverse Events (TEAEs) Baseline through the end of randomized period -up to 14 months per participant 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 32 weeks 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 98 weeks Defined as the time when treatment is discontinued
Duration of Response 142 weeks 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 Between 32 and 52 weeks 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 52 weeks 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.
Trial Locations
- Locations (26)
Columbia Weill Cornell Cancer Centers - Herbert Irving Comprehensive Cancer Center (HICCC)
🇺🇸New York, New York, United States
Ventura County Hematology-Oncology Specialists
🇺🇸Oxnard, California, United States
Tift Regional
🇺🇸Tifton, Georgia, United States
Edward Cancer Center
🇺🇸Naperville, Illinois, United States
INTEGRIS Southwest Medical Center
🇺🇸Oklahoma City, Oklahoma, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Waverly Hem Onc
🇺🇸Cary, North Carolina, United States
Innovative Clinical Research Institute
🇺🇸Whittier, California, United States
Summit Medical Group
🇺🇸Morristown, New Jersey, United States
Clinical Trials of SWLA LLC
🇺🇸Lake Charles, Louisiana, United States
Southern Illinois University
🇺🇸Springfield, Illinois, United States
Pacific Shores Medical Group
🇺🇸Long Beach, California, United States
Bond Clinic, PA
🇺🇸Winter Haven, Florida, United States
Compassionate Cancer Care Medical Group
🇺🇸Riverside, California, United States
Mayo Clinic
🇺🇸Phoenix, Arizona, United States
University of Southern California
🇺🇸Los Angeles, California, United States
North Shore Cancer Research Association-Skokie
🇺🇸Skokie, Illinois, United States
Gabrail Cancer Center- Canton Facility
🇺🇸Canton, Ohio, United States
Kaiser Permanente Northwest
🇺🇸Portland, Oregon, United States
Vidant Medical Center
🇺🇸Greenville, North Carolina, United States
INTEGRIS Cancer Institute Proton Campus
🇺🇸Oklahoma City, Oklahoma, United States
Renovatio Clinical
🇺🇸The Woodlands, Texas, United States
Geisinger - Knapper Clinic
🇺🇸Danville, Pennsylvania, United States
Prairie Lakes Health Care System Inc.
🇺🇸Watertown, South Dakota, United States
St. Agnes Hospital
🇺🇸Baltimore, Maryland, United States
Montefiore Medical Center
🇺🇸Bronx, New York, United States