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

MPN (Myeloproliferative Neoplasms) Clinical Trial

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)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03123588
• Other study ID #: INCB 18424-272 (RESET-272)
• Status: Terminated
• Phase: Phase 2
• Start date: November 14, 2017
• Est. completion date: August 3, 2020

Study information

• Verified date: October 2021
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 12
• Est. completion date: August 3, 2020
• Est. primary completion date: August 3, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• MPN (Myeloproliferative Neoplasms)
• Myeloproliferative Disorders
• Thrombocythemia, Essential
• Thrombocytosis

Intervention

Drug:
• Ruxolitinib
Ruxolitinib administered orally twice daily (BID) at the protocol-defined starting dose.
• Anagrelide
Anagrelide administered orally at a starting dose of 1 mg BID.
• Placebo
Anagrelide-placebo administered orally BID
• Placebo
Ruxolitinib-placebo administered orally BID.

Locations

Country	Name	City	State
United States	St. Agnes Hospital	Baltimore	Maryland
United States	Montefiore Medical Center	Bronx	New York
United States	Gabrail Cancer Center- Canton Facility	Canton	Ohio
United States	Waverly Hem Onc	Cary	North Carolina
United States	Geisinger - Knapper Clinic	Danville	Pennsylvania
United States	Vidant Medical Center	Greenville	North Carolina
United States	Clinical Trials of SWLA LLC	Lake Charles	Louisiana
United States	Pacific Shores Medical Group	Long Beach	California
United States	University of Southern California	Los Angeles	California
United States	Summit Medical Group	Morristown	New Jersey
United States	Edward Cancer Center	Naperville	Illinois
United States	Columbia Weill Cornell Cancer Centers - Herbert Irving Comprehensive Cancer Center (HICCC)	New York	New York
United States	INTEGRIS Cancer Institute Proton Campus	Oklahoma City	Oklahoma
United States	INTEGRIS Southwest Medical Center	Oklahoma City	Oklahoma
United States	Ventura County Hematology-Oncology Specialists	Oxnard	California
United States	Mayo Clinic	Phoenix	Arizona
United States	Kaiser Permanente Northwest	Portland	Oregon
United States	Compassionate Cancer Care Medical Group	Riverside	California
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	North Shore Cancer Research Association-Skokie	Skokie	Illinois
United States	Southern Illinois University	Springfield	Illinois
United States	Renovatio Clinical	The Woodlands	Texas
United States	Tift Regional	Tifton	Georgia
United States	Prairie Lakes Health Care System Inc.	Watertown	South Dakota
United States	Innovative Clinical Research Institute	Whittier	California
United States	Bond Clinic, PA	Winter Haven	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Time to Treatment Discontinuation	Defined as the time when treatment is discontinued	98 weeks
Secondary	Duration of Response	Defined as measurement of response from the onset of response to the loss of response for responders.	142 weeks
Secondary	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
Secondary	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