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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03123588
Recruitment Status : Terminated (Enrollment issues)
First Posted : April 21, 2017
Results First Posted : November 19, 2021
Last Update Posted : November 19, 2021
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
MPN (Myeloproliferative Neoplasms) Drug: Ruxolitinib Drug: Anagrelide Drug: Placebo Phase 2

Expanded Access : An investigational treatment associated with this study has been approved for sale to the public.   More info ...

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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)
Actual Study Start Date : November 14, 2017
Actual Primary Completion Date : August 3, 2020
Actual Study Completion Date : August 3, 2020


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

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: Anagrelide
Anagrelide administered orally at a starting dose of 1 mg BID.

Drug: Placebo
Ruxolitinib-placebo administered orally BID.




Primary Outcome Measures :
  1. Proportion of Subjects Who Achieve Platelet and White Blood Cell (WBC) Control [ Time Frame: 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 :
  1. Number of Participants With Treatment Emergent Adverse Events (TEAEs) [ Time Frame: 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.

  2. Proportion of Subjects Who Achieve Complete Remission or Partial Remission [ Time Frame: 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.


  3. Time to Treatment Discontinuation [ Time Frame: 98 weeks ]
    Defined as the time when treatment is discontinued

  4. Duration of Response [ Time Frame: 142 weeks ]
    Defined as measurement of response from the onset of response to the loss of response for responders.

  5. Proportion of Subjects Who Achieve Reduction of Platelet Counts to < 600 × 10^9/L [ Time Frame: 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.

  6. Proportion of Subjects Who Achieve a Reduction of WBC Counts to < 10 × 109/L [ Time Frame: 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03123588


Locations
Show Show 26 study locations
Sponsors and Collaborators
Incyte Corporation
Investigators
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Study Director: Albert Assad, MD Incyte Corporation
  Study Documents (Full-Text)

Documents provided by Incyte Corporation:
Study Protocol  [PDF] August 2, 2019
Statistical Analysis Plan  [PDF] September 24, 2019

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Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT03123588    
Other Study ID Numbers: INCB 18424-272 (RESET-272)
First Posted: April 21, 2017    Key Record Dates
Results First Posted: November 19, 2021
Last Update Posted: November 19, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Incyte Corporation:
Essential thrombocythemia
hydroxyurea-resistant
hydroxyurea-intolerant
ruxolitinib
anagrelide
Additional relevant MeSH terms:
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Myeloproliferative Disorders
Thrombocytosis
Thrombocythemia, Essential
Bone Marrow Diseases
Hematologic Diseases
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders
Anagrelide
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors