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.
Brief Title
Phase 2 Study of Ruxolitinib Versus Anagrelide in Subjects With Essential Thrombocythemia Who Are Resistant to or Intolerant of Hydroxyurea (RESET-272)
Categories
Completion Date
Completion Date Type
Actual
Conditions
MPN (Myeloproliferative Neoplasms)
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).
1. 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).
2. 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.
* 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).
1. 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).
2. 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.
Inclusion 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.
* 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.
Gender
All
Gender Based
false
Keywords
Essential thrombocythemia
hydroxyurea-resistant
hydroxyurea-intolerant
ruxolitinib
anagrelide
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT03123588
Org Class
Industry
Org Full Name
Incyte Corporation
Org Study Id
INCB 18424-272 (RESET-272)
Overall Status
Terminated
Phases
Phase 2
Primary Completion Date
Primary Completion Date Type
Actual
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)
Primary Outcomes
Outcome 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.
Outcome Measure
Proportion of Subjects Who Achieve Platelet and White Blood Cell (WBC) Control
Outcome Time Frame
52 weeks
Secondary Outcomes
Outcome Description
Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.
Outcome Time Frame
Baseline through the end of randomized period -up to 14 months per participant
Outcome Measure
Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Outcome 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.
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.
Outcome Time Frame
32 weeks
Outcome Measure
Proportion of Subjects Who Achieve Complete Remission or Partial Remission
Outcome Description
Defined as the time when treatment is discontinued
Outcome Time Frame
98 weeks
Outcome Measure
Time to Treatment Discontinuation
Outcome Description
Defined as measurement of response from the onset of response to the loss of response for responders.
Outcome Time Frame
142 weeks
Outcome Measure
Duration of Response
Outcome 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.
Outcome Time Frame
Between 32 and 52 weeks
Outcome Measure
Proportion of Subjects Who Achieve Reduction of Platelet Counts to < 600 × 10^9/L
Outcome 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.
Outcome Time Frame
52 weeks
Outcome Measure
Proportion of Subjects Who Achieve a Reduction of WBC Counts to < 10 × 109/L
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Swati Goel
Investigator Email
swgoel@montefiore.org
Investigator Phone
718-920-6310 / 718-920-4137
Categories Mesh Debug
Blood & Bone Marrow Cancers --- MYELOPROLIFERATIVE DISORDERS
Blood & Bone Marrow Cancers --- BONE MARROW DISEASES
Blood Disorders --- HEMATOLOGIC DISEASES
Blood & Bone Marrow Cancers --- HEMATOLOGIC DISEASES
Blood Disorders --- BLOOD COAGULATION DISORDERS
Blood Disorders --- BLOOD PLATELET DISORDERS
Blood & Bone Marrow Cancers --- HEMORRHAGIC DISORDERS
MeSH Terms
MYELOPROLIFERATIVE DISORDERS
THROMBOCYTHEMIA, ESSENTIAL
BONE MARROW DISEASES
HEMATOLOGIC DISEASES
HEMIC AND LYMPHATIC DISEASES
BLOOD COAGULATION DISORDERS
THROMBOCYTOSIS
BLOOD PLATELET DISORDERS
HEMORRHAGIC DISORDERS
RUXOLITINIB
ANAGRELIDE
COUNTERFEIT DRUGS
SUBSTANDARD DRUGS
PHARMACEUTICAL PREPARATIONS