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

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)

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.

Study Overview

• Status: Terminated
• Conditions: MPN (Myeloproliferative Neoplasms)
• Intervention / Treatment: Drug: Ruxolitinib; Drug: Placebo; Drug: Placebo; Drug: Anagrelide

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2

Expanded Access

Approved for sale to the public. See expanded access record.

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • California
    • Long Beach, California, United States, 90813
      • Pacific Shores Medical Group
    • Los Angeles, California, United States, 90033
      • University of Southern California
    • Oxnard, California, United States, 93030
      • Ventura County Hematology-Oncology Specialists
    • Riverside, California, United States, 92501
      • Compassionate Cancer Care Medical Group
    • Whittier, California, United States, 90603
      • Innovative Clinical Research Institute
  • Florida
    • Winter Haven, Florida, United States, 33880
      • Bond Clinic, PA
  • Georgia
    • Tifton, Georgia, United States, 31794
      • Tift Regional
  • Illinois
    • Naperville, Illinois, United States, 60540
      • Edward Cancer Center
    • Skokie, Illinois, United States, 60076
      • North Shore Cancer Research Association-Skokie
    • Springfield, Illinois, United States, 62702
      • Southern Illinois University
  • Louisiana
    • Lake Charles, Louisiana, United States, 70601
      • Clinical Trials of Swla Llc
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • St. Agnes Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • Morristown, New Jersey, United States, 07960
      • Summit Medical Group
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10032
      • Columbia Weill Cornell Cancer Centers - Herbert Irving Comprehensive Cancer Center (HICCC)
  • North Carolina
    • Cary, North Carolina, United States, 27518
      • Waverly Hem Onc
    • Greenville, North Carolina, United States, 27858
      • Vidant Medical Center
  • Ohio
    • Canton, Ohio, United States, 44718
      • Gabrail Cancer Center- Canton Facility
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73109
      • Integris Southwest Medical Center
    • Oklahoma City, Oklahoma, United States, 73142
      • INTEGRIS Cancer Institute Proton Campus
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Northwest
  • Pennsylvania
    • Danville, Pennsylvania, United States, 17822
      • Geisinger - Knapper Clinic
  • South Dakota
    • Watertown, South Dakota, United States, 57201
      • Prairie Lakes Health Care System Inc.
  • Texas
    • The Woodlands, Texas, United States, 77401
      • Renovatio Clinical

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A : Ruxolitinib and anagrelide placebo; Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.	Drug: Ruxolitinib; Ruxolitinib administered orally twice daily (BID) at the protocol-defined starting dose.; Other Names: Jakafi; INCB018424; Drug: Placebo; Anagrelide-placebo administered orally BID; Drug: Placebo; Ruxolitinib-placebo administered orally BID.
Active Comparator: Group B : Anagrelide and Ruxolitinib 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.	Drug: Placebo; Anagrelide-placebo administered orally BID; Drug: Placebo; Ruxolitinib-placebo administered orally BID.; Drug: Anagrelide; Anagrelide administered orally at a starting dose of 1 mg BID.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of Subjects Who Achieve Platelet and White Blood Cell (WBC) Control	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.	52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.	Baseline through the end of randomized period -up to 14 months per participant
Proportion of Subjects Who Achieve Complete Remission or Partial Remission	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.	32 weeks
Time to Treatment Discontinuation	Defined as the time when treatment is discontinued	98 weeks
Duration of Response	Defined as measurement of response from the onset of response to the loss of response for responders.	142 weeks
Proportion of Subjects Who Achieve Reduction of Platelet Counts to < 600 × 10^9/L	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.	Between 32 and 52 weeks
Proportion of Subjects Who Achieve a Reduction of WBC Counts to < 10 × 109/L	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.	52 weeks

Collaborators and Investigators

• Sponsor: Incyte Corporation

Study record dates

Study Major Dates

• Study Start (Actual): November 14, 2017
• Primary Completion (Actual): August 3, 2020
• Study Completion (Actual): August 3, 2020

Study Registration Dates

• First Submitted: April 17, 2017
• First Submitted That Met QC Criteria: April 19, 2017
• First Posted (Actual): April 21, 2017

Study Record Updates

• Last Update Posted (Actual): November 19, 2021
• Last Update Submitted That Met QC Criteria: October 21, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: ruxolitinib; Essential thrombocythemia; anagrelide; hydroxyurea-resistant; hydroxyurea-intolerant
• Additional Relevant MeSH Terms: Bone Marrow Diseases; Hematologic Diseases; Hemorrhagic Disorders; Blood Coagulation Disorders; Blood Platelet Disorders; Thrombocytosis; Thrombocythemia, Essential; Myeloproliferative Disorders; Molecular Mechanisms of Pharmacological Action; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Anagrelide
• Other Study ID Numbers: INCB 18424-272 (RESET-272)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No