Trial Outcomes & Findings for Phase 2 Study of Ruxolitinib Versus Anagrelide in Subjects With Essential Thrombocythemia Who Are Resistant to or Intolerant of Hydroxyurea (RESET-272) (NCT NCT03123588)

Last Updated: 2021-11-19

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

12 participants

Primary outcome timeframe

52 weeks

Results posted on

2021-11-19

Participant Flow

Approximately 120 participants were planned for enrollment and 12 participants were enrolled (6 in the ruxolitinib group and 6 in the anagrelide group). The first participant was dosed on 14 Nov 2017 and Last participant completed study on 03 Aug 2020

Twelve participants were enrolled and randomized. One participant in the ruxolitinib group was enrolled in error and withdrawn from the study before receiving any dose of study drug.

Participant milestones

Participant milestones
Measure	Group A : Ruxolitinib and Anagrelide Placebo Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.	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.
Overall Study STARTED	6	6
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	6	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A : Ruxolitinib and Anagrelide Placebo Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.	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.
Overall Study Study Terminated by Sponsor	2	5
Overall Study Withdrawal by Subject	1	0
Overall Study Adverse Event	1	0
Overall Study Physician Decision	2	1

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A : Ruxolitinib and Anagrelide Placebo n=6 Participants Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.	Group B : Anagrelide and Ruxolitinib Placebo n=6 Participants 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.	Total n=12 Participants Total of all reporting groups
Age, Continuous	71.8 years STANDARD_DEVIATION 13.04 • n=5 Participants	61.2 years STANDARD_DEVIATION 16.77 • n=7 Participants	66.5 years STANDARD_DEVIATION 15.37 • n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	6 Participants n=5 Participants	5 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized White/Caucasian	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants

PRIMARY outcome

Timeframe: 52 weeks

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

Outcome measures

Outcome measures
Measure	Group A : Ruxolitinib and Anagrelide Placebo n=6 Participants Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.	Group B : Anagrelide and Ruxolitinib PLacebo n=6 Participants 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.
Proportion of Subjects Who Achieve Platelet and White Blood Cell (WBC) Control	0 proportion of participants	0.17 proportion of participants

SECONDARY outcome

Timeframe: Baseline through the end of randomized period -up to 14 months per participant

Population: The safety population includes all randomized subjects who received at least 1 dose of study drug. AE has been summarized only in randomized period. End of randomized period is defined as the earliest of discontinuation or the individual unblinding date.

Adverse events reported for the first time or worsening of a pre-existing event after first dose of study drug/treatment.

Outcome measures

Outcome measures
Measure	Group A : Ruxolitinib and Anagrelide Placebo n=5 Participants Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.	Group B : Anagrelide and Ruxolitinib PLacebo n=6 Participants 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.
Number of Participants With Treatment Emergent Adverse Events (TEAEs)	5 participants	4 participants

SECONDARY outcome

Timeframe: 32 weeks

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

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.

Outcome measures

Outcome measures
Measure	Group A : Ruxolitinib and Anagrelide Placebo n=6 Participants Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.	Group B : Anagrelide and Ruxolitinib PLacebo n=6 Participants 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.
Proportion of Subjects Who Achieve Complete Remission or Partial Remission	0 proportion of participants	0.17 proportion of participants

SECONDARY outcome

Timeframe: 98 weeks

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

Defined as the time when treatment is discontinued

Outcome measures

Outcome measures
Measure	Group A : Ruxolitinib and Anagrelide Placebo n=5 Participants Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.	Group B : Anagrelide and Ruxolitinib PLacebo n=6 Participants 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.
Time to Treatment Discontinuation	261.2 Days Standard Deviation 238.85	437.2 Days Standard Deviation 183.99

SECONDARY outcome

Timeframe: 142 weeks

Population: The intent-to-treat (ITT) population who are responders

Defined as measurement of response from the onset of response to the loss of response for responders.

Outcome measures

Outcome measures
Measure	Group A : Ruxolitinib and Anagrelide Placebo Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.	Group B : Anagrelide and Ruxolitinib PLacebo n=1 Participants 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.
Duration of Response	—	442 Days

SECONDARY outcome

Timeframe: Between 32 and 52 weeks

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

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.

Outcome measures

Outcome measures
Measure	Group A : Ruxolitinib and Anagrelide Placebo n=5 Participants Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.	Group B : Anagrelide and Ruxolitinib PLacebo n=6 Participants 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.
Proportion of Subjects Who Achieve Reduction of Platelet Counts to < 600 × 10^9/L	0 Proportion of participants	0.50 Proportion of participants

SECONDARY outcome

Timeframe: 52 weeks

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

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.

Outcome measures

Outcome measures
Measure	Group A : Ruxolitinib and Anagrelide Placebo n=5 Participants Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.	Group B : Anagrelide and Ruxolitinib PLacebo n=6 Participants 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.
Proportion of Subjects Who Achieve a Reduction of WBC Counts to < 10 × 109/L	0 Proportion of participants	0.33 Proportion of participants

Adverse Events

Group A : Ruxolitinib and Anagrelide Placebo

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Group B : Anagrelide and Ruxolitinib Placebo

Serious events: 1 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Group A : Ruxolitinib and Anagrelide Placebo n=5 participants at risk Ruxolitinib or placebo will be administered orally twice a day at a starting dose of 10 mg.	Group B : Anagrelide and Ruxolitinib Placebo n=6 participants at risk 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
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Non-small cell lung cancer	0.00% 0/5 • Baseline through the end of randomized period -up to 14 months per participant The safety population includes all randomized subjects who received at least 1 dose of study drug. AE has been summarized only in randomized period. End of randomized period is defined as the earliest of discontinuation or the individual unblinding date.	16.7% 1/6 • Number of events 1 • Baseline through the end of randomized period -up to 14 months per participant The safety population includes all randomized subjects who received at least 1 dose of study drug. AE has been summarized only in randomized period. End of randomized period is defined as the earliest of discontinuation or the individual unblinding date.

Other adverse events

Additional Information

Call Center

Incyte Corporation

Phone: 1.855.463.3463

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Clinical Study Agreement
Publication restrictions are in place

Restriction type: OTHER