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

Phase 2

Terminated

• Conditions: MPN (Myeloproliferative Neoplasms)
• Interventions: Drug: Ruxolitinib; Drug: Anagrelide; Drug: Placebo

• Registration Number: NCT03123588
• Lead Sponsor: Incyte Corporation

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-04-17
• Study First Submitted QC: 2017-04-19
• Study First Posted: 2017-04-21
• Study Start: 2017-11-14
• Primary Completion: 2020-08-03
• Study Completion: 2020-08-03
• Results First Submitted: 2021-08-02
• Status Verified: 2021-10
• Results First Submitted QC: 2021-10-21
• Last Update Submitted: 2021-10-21
• Results First Posted: 2021-11-19
• Last Update Posted: 2021-11-19

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A : Ruxolitinib and anagrelide placebo	Ruxolitinib	Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.
Group A : Ruxolitinib and anagrelide placebo	Placebo	Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.
Group B : Anagrelide and Ruxolitinib PLacebo	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.
Group B : Anagrelide and Ruxolitinib PLacebo	Anagrelide	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.

Primary Outcome Measures

Name	Time	Method
Proportion of Subjects Who Achieve Platelet and White Blood Cell (WBC) Control	52 weeks	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.

Secondary Outcome Measures

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

Trial Locations

Locations (26)

Mayo Clinic; 🇺🇸 Phoenix, Arizona, United States

Pacific Shores Medical Group; 🇺🇸 Long Beach, California, United States

University of Southern California; 🇺🇸 Los Angeles, California, United States

Ventura County Hematology-Oncology Specialists; 🇺🇸 Oxnard, California, United States

Compassionate Cancer Care Medical Group; 🇺🇸 Riverside, California, United States

Innovative Clinical Research Institute; 🇺🇸 Whittier, California, United States

Bond Clinic, PA; 🇺🇸 Winter Haven, Florida, United States

Tift Regional; 🇺🇸 Tifton, Georgia, United States

Edward Cancer Center; 🇺🇸 Naperville, Illinois, United States

North Shore Cancer Research Association-Skokie; 🇺🇸 Skokie, Illinois, United States

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