Phase 2 Study of Ruxolitinib Versus Anagrelide in Subjects With Essential Thrombocythemia Who Are Resistant to or Intolerant of Hydroxyurea (RESET-272)

Incyte

Status and phase: Terminated; Phase 2

Conditions: MPN (Myeloproliferative Neoplasms)

Treatments: Drug: Anagrelide; Drug: Ruxolitinib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT03123588

INCB 18424-272 (RESET-272)

Details and patient eligibility

About

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.

Enrollment: 12 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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12 participants in 2 patient groups

Group A : Ruxolitinib and anagrelide placebo

Experimental group

Description:

Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.

Treatment:

Drug: Ruxolitinib

Drug: Placebo

Drug: Placebo

Group B : Anagrelide and Ruxolitinib PLacebo

Active Comparator group

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.

Treatment:

Drug: Anagrelide

Drug: Placebo

Drug: Placebo