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Alternative Dosing Strategy of Ruxolitinib in Patients With Myelofibrosis

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ClinicalTrials.gov Identifier: NCT01445769
Recruitment Status : Completed
First Posted : October 4, 2011
Results First Posted : September 19, 2014
Last Update Posted : September 19, 2014
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Primary Myelofibrosis
Post-Polycythemia Vera Myelofibrosis
Post-Essential Thrombocythemia Myelofibrosis
Intervention Drug: Ruxolitinib
Enrollment 45
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Ruxolitinib
Hide Arm/Group Description Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported Patients' Global Impression of Change (PGIC) score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Period Title: Overall Study
Started 45
Completed 37
Not Completed 8
Reason Not Completed
Consent Withdrawn             2
Disease Progression             1
Lost to Follow-up             5
Arm/Group Title Ruxolitinib
Hide Arm/Group Description Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥ 100 x 10^9/L at week 12 or ≥ 150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Baseline Participants 45
Hide Baseline Analysis Population Description
Intent-to-treat population: All enrolled participants. Note that this was a pilot study which was not sufficiently powered.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 45 participants
70.2  (9.10)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants
Female
21
  46.7%
Male
24
  53.3%
1.Primary Outcome
Title Mean Percentage Change From Baseline in Spleen Volume at Week 24
Hide Description Spleen volume was measured using magnetic resonance imaging (MRI) or computed tomography (CT) scan. The MRIs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. MRI was the preferred method for obtaining spleen volume data. CT scans were performed if the participant was not a candidate for MRI. The CT scans were processed by the same central laboratory used for MRIs. The same method (MRI or CT) was used for all visits for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants. Note that 2 subjects did not have the Week 24 MRI; one subject dropped out for disease progression and two withdrew consent prior to the Week 24 MRI. Thus 40 subjects were analyzed.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia. Only the subjects who had Week 24 spleen volume data are summarized.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: Percentage change
-14.9  (21.06)
2.Primary Outcome
Title Median Percent Change From Baseline in Spleen Volume at Week 24
Hide Description Spleen volume was measured using magnetic resonance imaging (MRI) or computed tomography (CT) scan. The MRIs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. MRI was the preferred method for obtaining spleen volume data. CT scans were performed if the participant was not a candidate for MRI. The CT scans were processed by the same central laboratory used for MRIs. The same method (MRI or CT) was used for all visits for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants. Note that 2 subjects did not have the Week 24 MRI; one subject dropped out for disease progression and two withdrew consent prior to the Week 24 MRI. Thus 40 subjects were analyzed.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia. Only the subjects who had Week 24 spleen volume data are summarized.
Overall Number of Participants Analyzed 40
Median (Full Range)
Unit of Measure: : Percentage change
-17.3
(-54.2 to 58.5)
3.Secondary Outcome
Title Mean Percentage Change From Baseline in the Total Symptom Score at Week 24
Hide Description Symptoms of myelofibrosis were assessed using a symptom diary, the modified Myelofibrosis Symptom Assessment Form (MFSAF v2.0). Participants were issued a hand-held device to record answers to queries regarding 7 symptoms of myelofibrosis each night from Baseline through Week 24. Symptoms assessed included night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), muscle/bone pain, and inactivity. The daily total symptom score (TSS) was the sum of the first 6 individual symptom scores (each on a scale of 0-10). Inactivity was not included in the total score. The Baseline TSS was the mean of daily total symptom scores from the last 7 consecutive days prior to the first study dose and ranged from 0 to 60. The Week 24 TSS was the mean of the daily total symptom scores from the last 28 consecutive days prior to the Week 24 visit and ranged from 0 to 60. A higher score indicates worse symptoms. A negative change score indicates improvement.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants. Note that 3 subjects did not have the Week 24 TSS; one subject dropped out for disease progression and two withdrew consent prior to the Week 24 TSS assessment. Thus 39 subjects were analyzed.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Participants Analyzed 39
Mean (Standard Deviation)
Unit of Measure: Percentage change
-34.3  (69.05)
4.Secondary Outcome
Title Median Percent Change From Baseline in the Total Symptom Score at Week 24
Hide Description Symptoms of myelofibrosis were assessed using a symptom diary, the modified MFSAF v2.0. Participants were issued a hand-held device to record answers to queries regarding 7 symptoms of myelofibrosis each night from Baseline through Week 24. Symptoms assessed included night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), muscle/bone pain, and inactivity. The daily TSS was the sum of the first 6 individual symptom scores (each on a scale of 0-10). Inactivity was not included in the total score. The Baseline total symptom score was the mean of daily total symptom scores from the last 7 consecutive days prior to the first study dose and ranged from 0 to 60. The Week 24 total symptom score was the mean of the daily total symptom scores from the last 28 consecutive days prior to the Week 24 visit and ranged from 0 to 60. A higher score indicates worse symptoms. A negative change score indicates improvement.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants. Note that 3 subjects did not have the Week 24 TSS; one subject dropped out for disease progression and two withdrew consent prior to the Week 24 TSS assessment. Thus 39 subjects were analyzed.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Participants Analyzed 39
Median (Full Range)
Unit of Measure: Percentage change
-45.6
(-100.0 to 261.9)
5.Secondary Outcome
Title Percentage of Participants With a ≥ 35% Reduction From Baseline in Spleen Volume at Week 24
Hide Description Spleen volume was measured using magnetic resonance imaging (MRI) or computed tomography (CT) scan. The MRIs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. MRI was the preferred method for obtaining spleen volume data. CT scans were performed if the participant was not a candidate for MRI. The CT scans were processed by the same central laboratory used for MRIs. The same method (MRI or CT) was used for all visits for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Participants Analyzed 45
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
15.6
(6.5 to 29.5)
6.Secondary Outcome
Title Percentage of Participants With a ≥ 10% Reduction From Baseline in Spleen Volume at Week 24
Hide Description Spleen volume was measured using magnetic resonance imaging (MRI) or computed tomography (CT) scan. The MRIs were read in the central imaging laboratory. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the technique of least squares. MRI was the preferred method for obtaining spleen volume data. CT scans were performed if the participant was not a candidate for MRI. The CT scans were processed by the same central laboratory used for MRIs. The same method (MRI or CT) was used for all visits for a given participant unless a new contraindication to the use of MRI (eg, pacemaker insertion) occurred.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Participants Analyzed 45
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
57.8
(42.2 to 72.3)
7.Secondary Outcome
Title Percentage of Participants With a ≥ 50% Improvement From Baseline in Total Symptom Score at Week 24
Hide Description Symptoms of myelofibrosis were assessed using a symptom diary, the modified MFSAF v2.0. Participants were issued a hand-held device to record answers to queries regarding 7 symptoms of myelofibrosis each night from Baseline through Week 24. Symptoms assessed included night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), muscle/bone pain, and inactivity. The daily total symptom score was the sum of the first 6 individual symptom scores (each on a scale of 0-10). Inactivity was not included in the total score. The Baseline total symptom score was the mean of daily total symptom scores from the last 7 consecutive days prior to the first study dose and ranged from 0 to 60. The Week 24 total symptom score was the mean of the daily total symptom scores from the last 28 consecutive days prior to the Week 24 visit and ranged from 0 to 60. A higher score indicates worse symptoms. A negative change score indicates improvement.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Participants Analyzed 45
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
40.0
(25.7 to 55.7)
8.Secondary Outcome
Title Mean Percentage Change From Baseline in Palpable Spleen Length at Week 24
Hide Description Spleen length was assessed by manual palpation. The edge of the spleen was determined by palpation and measured in centimeters, using a soft ruler, from the costal margin to the point of greatest splenic protrusion.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants. Note that one subject had a non-palpable spleen at baseline, one subject did not have the Week 24 spleen palpation performed; one subject dropped out for disease progression and two withdrew consent prior to the Week 24 spleen palpation. Thus 40 subjects were analyzed.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Participants Analyzed 40
Mean (Standard Deviation)
Unit of Measure: Percentage change
-47.6  (42.05)
9.Secondary Outcome
Title Median Percent Change From Baseline in Palpable Spleen Length at Week 24
Hide Description Spleen length was assessed by manual palpation. The edge of the spleen was determined by palpation and measured in centimeters, using a soft ruler, from the costal margin to the point of greatest splenic protrusion.
Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants. Note that one subject had a non-palpable spleen at baseline, one subject did not have the Week 24 spleen palpation performed; one subject dropped out for disease progression and two withdrew consent prior to the Week 24 spleen palpation. Thus 40 subjects were analyzed.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Participants Analyzed 40
Median (Full Range)
Unit of Measure: Percentage change
-39.8
(-100.0 to 26.7)
10.Secondary Outcome
Title Percentage of Participants With a ≥ 50% Improvement From Baseline in Their Transfusion Status or With New Transfusion Independence Status for Those Participants Who Were Transfusion Dependent at Baseline
Hide Description

Transfusion dependence at Baseline is defined as subjects who received ≥ 2 units of red blood cell product(s) in the 12 consecutive weeks prior to the date of first dose.

Transfusion independence On-Study is defined as subjects who received 0 units of red blood cell products over any 12-week period after starting dosing with ruxolitinib.

Improvement in transfusion dependence On-Study is defined as a 50% or greater reduction in the frequency of red blood cell transfusions over any 12-week period after starting dosing with ruxolitinib.

Time Frame Baseline to Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants who were transfusion dependent at baseline (n=15).
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Participants Analyzed 15
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percentage of participants
20.0
(4.3 to 48.1)
11.Secondary Outcome
Title Percentage of Participants With Clinically Notable Anemia
Hide Description Clinically Notable Anemia was a pre-specified safety parameter examined at Weeks 12, 18 and 24 and defined as: 1) New onset Grade 3 or higher anemia in subjects who are transfusion independent at Baseline, 2) New onset transfusion dependence in subjects who are transfusion independent at Baseline, defined as receipt of ≥ 2 units in ≤ a 12-week interval, 3) 50% increase in transfusions compared to Baseline in subjects who are transfusion dependent at Baseline.
Time Frame Baseline to Weeks 12, 18 and 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population: All participants who took at least 1 dose of study drug.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: Percentage of participants
Week 12 33.3
Week 18 (n = 44) 27.3
Week 24 (n = 43) 27.9
12.Secondary Outcome
Title Mean Percentage Change in Abdominal Symptom Scores at Week 24.
Hide Description Symptoms of myelofibrosis were assessed using a symptom diary, the modified MFSAF v2.0. Participants were issued a hand-held device to record answers to queries regarding 7 symptoms of myelofibrosis each night from Baseline through Week 24. The abdominal symptom score was the sum of 3 individual symptom scores (abdominal discomfort, pain under ribs on left side, and feeling of fullness [early satiety]), each on a scale of 0 to 10. A higher score indicates worse symptoms. A negative change score indicates improvement. The Baseline abdominal symptom score was the mean of daily abdominal symptom scores from the last 7 consecutive days prior to the first study dose and ranged from 0 to 30. The Week 24 abdominal symptom score was the mean of the daily abdominal symptom scores from the last 28 consecutive days prior to the Week 24 visit and ranged from 0 to 30.
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants. Note that three subjects did not have the Week 24 TSS; one subject dropped out for disease progression and two withdrew consent prior to the Week 24 TSS assessment. Thus 39 subjects were analyzed.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Participants Analyzed 39
Mean (Standard Deviation)
Unit of Measure: Percentage change
-33.2  (69.83)
13.Secondary Outcome
Title Median Percentage Change in Abdominal Symptom Scores at Week 24.
Hide Description Symptoms of myelofibrosis were assessed using a symptom diary, the modified MFSAF v2.0. Participants were issued a hand-held device to record answers to queries regarding 7 symptoms of myelofibrosis each night from Baseline through Week 24. The abdominal symptom score was the sum of 3 individual symptom scores (abdominal discomfort, pain under ribs on left side, and feeling of fullness [early satiety]).
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants. Note that three subjects did not have the Week 24 TSS; one subject dropped out for disease progression and two withdrew consent prior to the Week 24 TSS assessment. Thus 39 subjects were analyzed.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Participants Analyzed 39
Median (Full Range)
Unit of Measure: Percentage change
-50.5
(-100.0 to 219.0)
14.Secondary Outcome
Title Number of Participants With Grade 3 or Grade 4 Adverse Events
Hide Description [Not Specified]
Time Frame Baseline to the end of the study
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety population: All participants who took at least 1 dose of study drug.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: participants
Anemia (Grade 3) 9
Thrombocytopenia (Grade 3) 1
Umbilical hernia (Grade 3) 1
Cholelithiasis (Grade 3) 1
Blood creatine phosphokinase increased (Grade 3) 1
Blood triglycerides increased (Grade 3) 1
Lipase increased (Grade 3) 1
Dehydration (Grade 3) 1
Hyperkalaemia (Grade 3) 1
Hypermagnesaemia (Grade 3) 1
Dizziness (Grade 3) 1
Myelodysplastic syndrome (Grade 4) 1
15.Other Pre-specified Outcome
Title Dose Distribution at Week 24
Hide Description Average Daily Dose for the last 28 days on study.
Time Frame Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Intent-to-treat population: All enrolled participants.
Arm/Group Title Ruxolitinib
Hide Arm/Group Description:
Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥ 100 x 10^9/L at week 12 or ≥ 150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: participants
0-5 mg 2
> 5-10 mg 14
> 10-20 mg 12
> 20-30 mg 12
> 30-40 mg 5
Time Frame From the first dose of study medication through the Follow-Up Visit.
Adverse Event Reporting Description Safety population: All participants who took at least 1 dose of study drug.
 
Arm/Group Title Ruxolitinib
Hide Arm/Group Description Participants initially received ruxolitinib 10 mg twice a day (bid). Dose increases of 5 mg bid were permitted at Weeks 12 and 18 for subjects who did not meet criteria for or have a dose hold over the prior 6 weeks, had a platelet count ≥100 x 10^9/L at week 12 or ≥150 x 10^9/L at week 18, and had a self-reported PGIC score of 3 (minimally improved) to 7 (very much worse) OR the subject's palpable spleen length had been reduced by less than 40% at that visit relative to Baseline. The maximum dose was 15 mg BID at Week 12 and 20 mg bid at Week 18. There were also protocol-required dose decreases for protocol-defined anemia and thrombocytopenia.
All-Cause Mortality
Ruxolitinib
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Ruxolitinib
Affected / at Risk (%)
Total   2/45 (4.44%) 
Hepatobiliary disorders   
Cholelithiasis  1  1/45 (2.22%) 
Metabolism and nutrition disorders   
Dehydration  1  1/45 (2.22%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Ruxolitinib
Affected / at Risk (%)
Total   42/45 (93.33%) 
Blood and lymphatic system disorders   
Anemia  1  12/45 (26.67%) 
Thrombocytopenia  1  8/45 (17.78%) 
Gastrointestinal disorders   
Abdominal distension  1  3/45 (6.67%) 
Abdominal pain  1  6/45 (13.33%) 
Constipation  1  4/45 (8.89%) 
Diarrhea  1  6/45 (13.33%) 
Nausea  1  8/45 (17.78%) 
Vomiting  1  3/45 (6.67%) 
General disorders   
Fatigue  1  10/45 (22.22%) 
Oedema peripheral  1  6/45 (13.33%) 
Pyrexia  1  3/45 (6.67%) 
Injury, poisoning and procedural complications   
Contusion  1  5/45 (11.11%) 
Metabolism and nutrition disorders   
Decreased appetite  1  4/45 (8.89%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  9/45 (20.00%) 
Back pain  1  5/45 (11.11%) 
Muscle spasms  1  6/45 (13.33%) 
Pain in extremity  1  6/45 (13.33%) 
Nervous system disorders   
Dizziness  1  7/45 (15.56%) 
Headache  1  3/45 (6.67%) 
Paresthesia  1  3/45 (6.67%) 
Psychiatric disorders   
Insomnia  1  3/45 (6.67%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  6/45 (13.33%) 
Dyspnea  1  3/45 (6.67%) 
Dyspnea exertional  1  4/45 (8.89%) 
Skin and subcutaneous tissue disorders   
Night sweats  1  3/45 (6.67%) 
Pruritus  1  3/45 (6.67%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (15.1)
This was a single arm pilot study. The patient population differed from Phase III studies of ruxolitinib in myelofibrosis and therefore comparisons to standard dosing cannot be made from this study.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.
Results Point of Contact
Name/Title: Study Director
Organization: Incyte Corporation
Phone: 855 463-3463
Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT01445769     History of Changes
Other Study ID Numbers: 18424-261
First Submitted: September 23, 2011
First Posted: October 4, 2011
Results First Submitted: March 31, 2014
Results First Posted: September 19, 2014
Last Update Posted: September 19, 2014