MPN (Myeloproliferative Neoplasms)Phase 2NCT03123588

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

A Phase 2 study testing Ruxolitinib and Anagrelide in people with MPN (Myeloproliferative Neoplasms), run by Incyte Corporation at 26 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: MPN (Myeloproliferative Neoplasms)
What is being tested?: Ruxolitinib and Anagrelide
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 12 participants
Where: 26 sitesUnited States
Study dates: 14 Nov 2017to 3 Aug 2020
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

Subjects previously treated with anagrelide or Hydroxyurea (HU).
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).
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 locations and contacts

26 sites in 1 country.

City, postcode or hospital

26 sites in 1 country

United States26 sites

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

Other trials in United States

About this study

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)

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.

Conditions: MPN (Myeloproliferative Neoplasms)
Being tested: Ruxolitinib, Anagrelide, Placebo
Keywords: Essential thrombocythemia, hydroxyurea-resistant, hydroxyurea-intolerant, ruxolitinib, anagrelide
Medical subject headings: Myeloproliferative Disorders, Thrombocythemia, Essential

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

RuxolitinibDrug
Also called Jakafi, INCB018424
Ruxolitinib administered orally twice daily (BID) at the protocol-defined starting dose.
AnagrelideDrug
Anagrelide administered orally at a starting dose of 1 mg BID.
PlaceboDrug
Anagrelide-placebo administered orally BID
PlaceboDrug
Ruxolitinib-placebo administered orally BID.

Study groups in NCT03123588
Study group	Role	What they receive
Group A : Ruxolitinib and anagrelide placebo	Experimental	Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg. Receives: Drug: Ruxolitinib; Drug: Placebo
Group B : Anagrelide and Ruxolitinib PLacebo	Active comparator	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. Receives: Drug: Anagrelide; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: 52 weeks

Secondary outcomes (6)

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.
Measured: 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.
Measured: 32 weeks
Time to Treatment Discontinuation
Defined as the time when treatment is discontinued
Measured: 98 weeks
Duration of Response
Defined as measurement of response from the onset of response to the loss of response for responders.
Measured: 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.
Measured: 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.
Measured: 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Nov 20173 Aug 2020

First posted21 Apr 2017
Study start14 Nov 2017
Primary completion3 Aug 2020
Study completion3 Aug 2020

Why it stopped: Enrollment issues

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for MPN (Myeloproliferative Neoplasms)Studies of the same condition, open and under way.
More trials run by Incyte CorporationThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 12 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03123588
Sponsor's protocol ID: INCB 18424-272 (RESET-272)
Status last verified: Oct 2021
First submitted: 17 Apr 2017
Last updated: 19 Nov 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No
Expanded access: Available

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All MPN (Myeloproliferative Neoplasms) trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

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)
ClinicalTrials.gov ID: NCT03123588
Acronym / sponsor ID: INCB 18424-272 (RESET-272)
Conditions: MPN (Myeloproliferative Neoplasms)
Keywords: Essential thrombocythemia, hydroxyurea-resistant, hydroxyurea-intolerant, ruxolitinib, anagrelide
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Enrollment issues
Enrolment: 12 participants (actual)
Lead sponsor: Incyte CorporationIndustry (pharma, biotech, devices)
Study start: 14 Nov 2017 (actual)
Primary completion: 3 Aug 2020 (actual)
Study completion: 3 Aug 2020 (actual)
First posted: 21 Apr 2017 (actual)
Results: Posted 19 Nov 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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 design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Group A : Ruxolitinib and anagrelide placebo	Experimental	Drug: Ruxolitinib, Drug: PlaceboRuxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.
Group B : Anagrelide and Ruxolitinib PLacebo	Active comparator	Drug: Anagrelide, Drug: PlaceboAnagrelide 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

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 ≥ 650 × 10^9/L at screening.
WBC ≥ 11.0 × 10^9/L at screening.

Key exclusion criteria (8 listed)

Subjects previously treated with anagrelide or Hydroxyurea (HU).
Inadequate liver function at screening and Day 1 (before drug administration) as demonstrated by:
Inadequate renal function at screening as demonstrated by creatinine clearance < 40 mL/min calculated by Cockcroft-Gault equation.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
RuxolitinibAlso: Jakafi, INCB018424Ruxolitinib administered orally twice daily (BID) at the protocol-defined starting dose.	Drug	Group A : Ruxolitinib and anagrelide placebo
AnagrelideAnagrelide administered orally at a starting dose of 1 mg BID.	Drug	Group B : Anagrelide and Ruxolitinib PLacebo
PlaceboAnagrelide-placebo administered orally BID	Drug	Group A : Ruxolitinib and anagrelide placebo
PlaceboRuxolitinib-placebo administered orally BID.	Drug	Group B : Anagrelide and Ruxolitinib PLacebo

Primary outcome

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.

6 secondary outcomes

Number of Participants With Treatment Emergent Adverse Events (TEAEs)
Time frame: Baseline through the end of randomized period -up to 14 months per participant
Proportion of Subjects Who Achieve Complete Remission or Partial Remission
Time frame: 32 weeks
Time to Treatment Discontinuation
Time frame: 98 weeks
Duration of Response
Time frame: 142 weeks
Proportion of Subjects Who Achieve Reduction of Platelet Counts to < 600 × 10^9/L
Time frame: Between 32 and 52 weeks
Proportion of Subjects Who Achieve a Reduction of WBC Counts to < 10 × 109/L
Time frame: 52 weeks

Results and safety

Results posted to the registry on 19 Nov 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group A : Ruxolitinib and Anagrelide Placebo	6	0
Group B : Anagrelide and Ruxolitinib Placebo	6	0

Primary outcome: Proportion of Subjects Who Achieve Platelet and White Blood Cell (WBC) Control

Time frame: 52 weeks. Number. Unit: proportion of participants

Measure	Group A : Ruxolitinib and Anagrelide Placebo n = 6	Group B : Anagrelide and Ruxolitinib PLacebo n = 6
Value	0	0.17

Population analysed: The intent-to-treat (ITT) population will include subjects randomized in the study

6 secondary outcomes are reported in the full results.

Adverse events

Time frame: Baseline through the end of randomized period -up to 14 months per participant. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group A : Ruxolitinib and Anagrelide Placebo	0 of 5 (0%)	5 of 5 (100%)	0 of 5
Group B : Anagrelide and Ruxolitinib Placebo	1 of 6 (16.7%)	4 of 6 (66.7%)	0 of 6

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Nov 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: No

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RecruitingPhase 1
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Albert Assad, MD study director

Incyte Corporation

26 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Ruxolitinib and Anagrelide in people with MPN (Myeloproliferative Neoplasms), run by Incyte Corporation at 26 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 19 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 19 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Proportion of Subjects Who Achieve Platelet and White Blood Cell (WBC) Control (time frame: 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03123588.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Nov 2021.