Phase 2 Study of Ruxolitinib Versus Anagrelide in Subjects With Essential Thrombocythemia Who Are Resistant to or Intolerant of Hydroxyurea (RESET-272)
Condition: MPN (Myeloproliferative Neoplasms)
MeSH terms: Myeloproliferative Disorders; Thrombocytosis; Thrombocythemia, Essential
Intervention: Ruxolitinib; Anagrelide; Placebo; Placebo
Intervention description: Ruxolitinib administered orally twice daily (BID) at the protocol-defined starting dose.; Anagrelide administered orally at a starting dose of 1 mg BID.; Anagrelide-placebo administered orally BID; Ruxolitinib-placebo administered orally BID.
Intervention MeSH terms: Anagrelide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 12.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Essential thrombocythemia; hydroxyurea-resistant; hydroxyurea-intolerant; ruxolitinib; anagrelide

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.