Trial Outcomes & Findings for Alternative Dosing Strategy of Ruxolitinib in Patients With Myelofibrosis (NCT NCT01445769)
NCT ID: NCT01445769
Last Updated: 2019-03-27
Results Overview
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.
COMPLETED
PHASE2
45 participants
Baseline to Week 24
2019-03-27
Participant Flow
Participant milestones
| Measure |
Ruxolitinib
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.
|
|---|---|
|
Overall Study
STARTED
|
45
|
|
Overall Study
COMPLETED
|
37
|
|
Overall Study
NOT COMPLETED
|
8
|
Reasons for withdrawal
| Measure |
Ruxolitinib
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.
|
|---|---|
|
Overall Study
Consent Withdrawn
|
2
|
|
Overall Study
Disease Progression
|
1
|
|
Overall Study
Lost to Follow-up
|
5
|
Baseline Characteristics
Alternative Dosing Strategy of Ruxolitinib in Patients With Myelofibrosis
Baseline characteristics by cohort
| Measure |
Ruxolitinib
n=45 Participants
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.
|
|---|---|
|
Age, Continuous
|
70.2 years
STANDARD_DEVIATION 9.10 • n=99 Participants
|
|
Sex: Female, Male
Female
|
21 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Baseline to Week 24Population: 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.
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.
Outcome measures
| Measure |
Ruxolitinib
n=40 Participants
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.
|
|---|---|
|
Mean Percentage Change From Baseline in Spleen Volume at Week 24
|
-14.9 Percentage change
Standard Deviation 21.06
|
PRIMARY outcome
Timeframe: Baseline to Week 24Population: 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.
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.
Outcome measures
| Measure |
Ruxolitinib
n=40 Participants
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.
|
|---|---|
|
Median Percent Change From Baseline in Spleen Volume at Week 24
|
-17.3 : Percentage change
Interval -54.2 to 58.5
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: 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.
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.
Outcome measures
| Measure |
Ruxolitinib
n=39 Participants
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.
|
|---|---|
|
Mean Percentage Change From Baseline in the Total Symptom Score at Week 24
|
-34.3 Percentage change
Standard Deviation 69.05
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: 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.
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.
Outcome measures
| Measure |
Ruxolitinib
n=39 Participants
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.
|
|---|---|
|
Median Percent Change From Baseline in the Total Symptom Score at Week 24
|
-45.6 Percentage change
Interval -100.0 to 261.9
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Intent-to-treat population: All enrolled participants.
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.
Outcome measures
| Measure |
Ruxolitinib
n=45 Participants
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.
|
|---|---|
|
Percentage of Participants With a ≥ 35% Reduction From Baseline in Spleen Volume at Week 24
|
15.6 Percentage of participants
Interval 6.5 to 29.5
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Intent-to-treat population: All enrolled participants.
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.
Outcome measures
| Measure |
Ruxolitinib
n=45 Participants
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.
|
|---|---|
|
Percentage of Participants With a ≥ 10% Reduction From Baseline in Spleen Volume at Week 24
|
57.8 Percentage of participants
Interval 42.2 to 72.3
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Intent-to-treat population: All enrolled participants.
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.
Outcome measures
| Measure |
Ruxolitinib
n=45 Participants
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.
|
|---|---|
|
Percentage of Participants With a ≥ 50% Improvement From Baseline in Total Symptom Score at Week 24
|
40.0 Percentage of participants
Interval 25.7 to 55.7
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: 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.
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.
Outcome measures
| Measure |
Ruxolitinib
n=40 Participants
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.
|
|---|---|
|
Mean Percentage Change From Baseline in Palpable Spleen Length at Week 24
|
-47.6 Percentage change
Standard Deviation 42.05
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: 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.
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.
Outcome measures
| Measure |
Ruxolitinib
n=40 Participants
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.
|
|---|---|
|
Median Percent Change From Baseline in Palpable Spleen Length at Week 24
|
-39.8 Percentage change
Interval -100.0 to 26.7
|
SECONDARY outcome
Timeframe: Baseline to Week 24Population: Intent-to-treat population: All enrolled participants who were transfusion dependent at baseline (n=15).
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.
Outcome measures
| Measure |
Ruxolitinib
n=15 Participants
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.
|
|---|---|
|
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
|
20.0 Percentage of participants
Interval 4.3 to 48.1
|
SECONDARY outcome
Timeframe: Baseline to Weeks 12, 18 and 24Population: Safety population: All participants who took at least 1 dose of study drug.
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.
Outcome measures
| Measure |
Ruxolitinib
n=45 Participants
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.
|
|---|---|
|
Percentage of Participants With Clinically Notable Anemia
Week 12
|
33.3 Percentage of participants
|
|
Percentage of Participants With Clinically Notable Anemia
Week 18
|
27.3 Percentage of participants
|
|
Percentage of Participants With Clinically Notable Anemia
Week 24
|
27.9 Percentage of participants
|
SECONDARY outcome
Timeframe: Week 24Population: 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.
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.
Outcome measures
| Measure |
Ruxolitinib
n=39 Participants
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.
|
|---|---|
|
Mean Percentage Change in Abdominal Symptom Scores at Week 24.
|
-33.2 Percentage change
Standard Deviation 69.83
|
SECONDARY outcome
Timeframe: Week 24Population: 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.
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 \[early satiety\]).
Outcome measures
| Measure |
Ruxolitinib
n=39 Participants
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.
|
|---|---|
|
Median Percentage Change in Abdominal Symptom Scores at Week 24.
|
-50.5 Percentage change
Interval -100.0 to 219.0
|
SECONDARY outcome
Timeframe: Baseline to the end of the studyPopulation: Safety population: All participants who took at least 1 dose of study drug.
Outcome measures
| Measure |
Ruxolitinib
n=45 Participants
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.
|
|---|---|
|
Number of Participants With Grade 3 or Grade 4 Adverse Events
Anemia (Grade 3)
|
9 participants
|
|
Number of Participants With Grade 3 or Grade 4 Adverse Events
Thrombocytopenia (Grade 3)
|
1 participants
|
|
Number of Participants With Grade 3 or Grade 4 Adverse Events
Umbilical hernia (Grade 3)
|
1 participants
|
|
Number of Participants With Grade 3 or Grade 4 Adverse Events
Cholelithiasis (Grade 3)
|
1 participants
|
|
Number of Participants With Grade 3 or Grade 4 Adverse Events
Blood creatine phosphokinase increased (Grade 3)
|
1 participants
|
|
Number of Participants With Grade 3 or Grade 4 Adverse Events
Blood triglycerides increased (Grade 3)
|
1 participants
|
|
Number of Participants With Grade 3 or Grade 4 Adverse Events
Lipase increased (Grade 3)
|
1 participants
|
|
Number of Participants With Grade 3 or Grade 4 Adverse Events
Dehydration (Grade 3)
|
1 participants
|
|
Number of Participants With Grade 3 or Grade 4 Adverse Events
Hyperkalaemia (Grade 3)
|
1 participants
|
|
Number of Participants With Grade 3 or Grade 4 Adverse Events
Hypermagnesaemia (Grade 3)
|
1 participants
|
|
Number of Participants With Grade 3 or Grade 4 Adverse Events
Dizziness (Grade 3)
|
1 participants
|
|
Number of Participants With Grade 3 or Grade 4 Adverse Events
Myelodysplastic syndrome (Grade 4)
|
1 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Week 24Population: Intent-to-treat population: All enrolled participants.
Average Daily Dose for the last 28 days on study.
Outcome measures
| Measure |
Ruxolitinib
n=45 Participants
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.
|
|---|---|
|
Dose Distribution at Week 24
0-5 mg
|
2 participants
|
|
Dose Distribution at Week 24
> 5-10 mg
|
14 participants
|
|
Dose Distribution at Week 24
> 10-20 mg
|
12 participants
|
|
Dose Distribution at Week 24
> 20-30 mg
|
12 participants
|
|
Dose Distribution at Week 24
> 30-40 mg
|
5 participants
|
Adverse Events
Ruxolitinib
Serious adverse events
| Measure |
Ruxolitinib
n=45 participants at risk
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.
|
|---|---|
|
Hepatobiliary disorders
Cholelithiasis
|
2.2%
1/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Metabolism and nutrition disorders
Dehydration
|
2.2%
1/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
Other adverse events
| Measure |
Ruxolitinib
n=45 participants at risk
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.
|
|---|---|
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Blood and lymphatic system disorders
Anemia
|
26.7%
12/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
17.8%
8/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Abdominal distension
|
6.7%
3/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Abdominal pain
|
13.3%
6/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Constipation
|
8.9%
4/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Diarrhea
|
13.3%
6/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Nausea
|
17.8%
8/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Gastrointestinal disorders
Vomiting
|
6.7%
3/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
General disorders
Fatigue
|
22.2%
10/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
General disorders
Oedema peripheral
|
13.3%
6/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
General disorders
Pyrexia
|
6.7%
3/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Injury, poisoning and procedural complications
Contusion
|
11.1%
5/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
8.9%
4/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
20.0%
9/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.1%
5/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
13.3%
6/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
13.3%
6/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Nervous system disorders
Dizziness
|
15.6%
7/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Nervous system disorders
Headache
|
6.7%
3/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Nervous system disorders
Paresthesia
|
6.7%
3/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Psychiatric disorders
Insomnia
|
6.7%
3/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
13.3%
6/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
6.7%
3/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea exertional
|
8.9%
4/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
6.7%
3/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
6.7%
3/45 • From the first dose of study medication through the Follow-Up Visit.
Safety population: All participants who took at least 1 dose of study drug.
|
Additional Information
Study Director
Incyte Corporation
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER