Clinical trial NCT03123588: 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
Overall status: TERMINATED
Phase: PHASE2
Conditions: MPN (Myeloproliferative Neoplasms)
Keywords: Essential thrombocythemia
hydroxyurea-resistant
hydroxyurea-intolerant
ruxolitinib
anagrelide
Lead sponsor: Incyte Corporation
Sponsor class: INDUSTRY
First posted: 2017-04-21
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Proportion of Subjects Who Achieve Platelet and White Blood Cell (WBC) Control
timeFrame: 52 weeks
Secondary outcomes:
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs)
timeFrame: Baseline through the end of randomized period -up to 14 months per participant
measure: Proportion of Subjects Who Achieve Complete Remission or Partial Remission
timeFrame: 32 weeks
measure: Time to Treatment Discontinuation
timeFrame: 98 weeks
measure: Duration of Response
timeFrame: 142 weeks
measure: Proportion of Subjects Who Achieve Reduction of Platelet Counts to < 600 × 10^9/L
timeFrame: Between 32 and 52 weeks
measure: Proportion of Subjects Who Achieve a Reduction of WBC Counts to < 10 × 109/L
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Long Beach
country: United States
facility: Pacific Shores Medical Group
state: California
city: Los Angeles
country: United States
facility: University of Southern California
state: California
city: Oxnard
country: United States
facility: Ventura County Hematology-Oncology Specialists
state: California
city: Riverside
country: United States
facility: Compassionate Cancer Care Medical Group
state: California
city: Whittier
country: United States
facility: Innovative Clinical Research Institute
state: California
city: Winter Haven
country: United States
facility: Bond Clinic, PA
state: Florida
city: Tifton
country: United States
facility: Tift Regional
state: Georgia
city: Naperville
country: United States
facility: Edward Cancer Center
state: Illinois
city: Skokie
country: United States
facility: North Shore Cancer Research Association-Skokie
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University
state: Illinois
city: Lake Charles
country: United States
facility: Clinical Trials of SWLA LLC
state: Louisiana
city: Baltimore
country: United States
facility: St. Agnes Hospital
state: Maryland
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
city: Morristown
country: United States
facility: Summit Medical Group
state: New Jersey
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Columbia Weill Cornell Cancer Centers - Herbert Irving Comprehensive Cancer Center (HICCC)
state: New York
city: Cary
country: United States
facility: Waverly Hem Onc
state: North Carolina
city: Greenville
country: United States
facility: Vidant Medical Center
state: North Carolina
city: Canton
country: United States
facility: Gabrail Cancer Center- Canton Facility
state: Ohio
city: Oklahoma City
country: United States
facility: INTEGRIS Southwest Medical Center
state: Oklahoma
city: Oklahoma City
country: United States
facility: INTEGRIS Cancer Institute Proton Campus
state: Oklahoma
city: Portland
country: United States
facility: Kaiser Permanente Northwest
state: Oregon
city: Danville
country: United States
facility: Geisinger - Knapper Clinic
state: Pennsylvania
city: Watertown
country: United States
facility: Prairie Lakes Health Care System Inc.
state: South Dakota
city: The Woodlands
country: United States
facility: Renovatio Clinical
state: Texas
Study officials:
affiliation: Incyte Corporation
name: Albert Assad, MD
role: STUDY_DIRECTOR
References: