Ruxolitinib (INCB018424) in Participants With Primary Myelofibrosis (PMF), Post Essential Thrombocythemia-myelofibrosis and Post Polycythemia Vera-myelofibrosis (PPV-MF)
Sponsor
Incyte Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT01348490
Collaborator
(none)
66
38
1
90.2
1.7
0
Study Details
Study Description
Brief Summary
To evaluate the effects of treatment with ruxolitinib (INCB018424) on spleen volume, symptoms and potential side effects in participants with PMF, PPV-MF and PET-MF who have platelet counts of 50 x 109/L to 100 x 109/L. It is anticipated that individualized dose optimization from the starting ruxolitinib level of 5 mg bid will be associated with reductions in splenomegaly, MF-associated symptoms and inflammatory cytokine levels.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
66 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An Open-Label Assessment of Safety and Efficacy of Ruxolitinib (INCB018424) in Subjects With Primary Myelofibrosis, Post- Essential Thrombocythemia Myelofibrosis, and Post-Polycythemia Vera Myelofibrosis Who Have Platelet Counts of 50 × 10^9/L to 100 × 10^9/L
Actual Study Start Date
:
Jun 15, 2011
Actual Primary Completion Date
:
Dec 19, 2018
Actual Study Completion Date
:
Dec 19, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Ruxolitinib 5 mg Participants began administration with 5 mg ruxolitinib twice daily (BID) orally. Beginning at the Week 4 visit, doses of ruxolitinib could be increased in 5 mg once a day (QD) increments every 4 weeks every 4 weeks not to exceed a dose of 25 mg BID. |
Drug: Ruxolitinib
Ruxolitinib (INCB018424), 5 mg bid
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Percent Change From Baseline in Spleen Volume at Week 24 by Final Titrated Dose [Baseline and Week 24]
Magnetic resonance imaging (MRI) of the upper and lower abdomen and pelvis was performed to assess spleen volumes. Computed tomography (CT) scan was performed if participant was not a candidate for MRI or if MRI was not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
- Percent Change From Baseline in Total Symptom Score (TSS) as Measured by the Modified Myelofibrosis Symptom Assessment Form (MFSAF) V2.0 Diary at Week 24 by Final Titrated Dose [Baseline and Week 24]
Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms.
- Percentage of Participants With Treatment-emergent Adverse Events (TEAE) [Up to Week 156]
TEAE was defined as adverse events that began or worsened from baseline after the first administration of the study drug. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
- Percentage of Participants With New Onset Grade 4 Thrombocytopenia Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE V4.03) [Up to Week 156]
Participants with platelet count between 50 and 100 × 10^9/L at the screening and/or baseline visit were enrolled in the study. Thrombocytopenia is defined as a condition with low blood platelet count. Grade 4 thrombocytopenia was platelet count < 25 × 10^9/L. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
- Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03 [Up to Week 156]
Hemorrhages were defined as any lower level terms by MedDRA included in the Standardized MedDRA Query (SMQ) for hemorrhage terms. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred.
Secondary Outcome Measures
- Percent Change in Spleen Volume at Week 24 Compared to Baseline [Baseline and Week 24]
MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant was not a candidate for MRI, or if MRI was not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
- Percent Change in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline [Baseline and Week 24]
Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms..
- Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline [Baseline and Week 24]
MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant is not a candidate for MRI, or if MRI is not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
- Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline [Baseline and Week 24]
MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant is not a candidate for MRI, or if MRI is not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs.
- Percentage of Participants With ≥ 50% Improvement in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline [Baseline and Week 24]
Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms.
- Change in Spleen Length Measured by Palpation [Up to Week 156]
Measurement of spleen length below the left costal margin was measured by palpation at each study visit. Investigators were provided with a soft centimeter ruler so that palpable spleen length was measured in centimeters and not in finger breadths. 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.
- Percent Change From Baseline in Spleen Length Measured by Palpation [Up to Week 156]
Measurement of spleen length below the left costal margin was measured by palpation at each study visit. Investigators were provided with a soft centimeter ruler so that palpable spleen length was measured in centimeters and not in finger breadths. 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.
- Patient Global Impression of Change (PGIC) Score at Each Visit [Up to Week 156]
Symptoms of myelofibrosis were assessed using the PGIC questionnaire. Using the questionnaire, patients rated the overall sense of treatment effect on their symptoms on a scale of 1 (very much improved)- 7(very much worse). The specific wording was: Since the start of the treatment you've received in this study, your myelofibrosis symptoms are: 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change, 5) Minimally worse, 6) Much worse, 7) Very much worse. A higher score indicates worse symptoms.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosed with PMF, PPV-MF or PET-MF as confirmed by bone marrow biopsy
-
Discontinuation of all drugs used to treat underlying MF disease at least 14 days prior to baseline visit
-
INR <= 1.5 or PTT value < 1.5 x upper limit of normal (ULN) at study entry
-
Hemoglobin level at least 6.5 g/dL at Screening visit
-
Willingness to be transfused to treat low hemoglobin levels
Exclusion Criteria:
-
Females who are pregnant, unable to comply with birth control use to avoid becoming pregnant or breastfeeding
-
Males who cannot comply with birth control use to avoid fathering a child
-
Platelet count < 50 x109/L or absolute neutrophil count (ANC) < 1 x109/L at the Screening visit
-
Inadequate liver or renal function; Intracranial bleeds or invasive malignancy over the previous 2 years - international normalized ratio (INR) laboratory values cannot be > 1.5 x upper limit of normal at study entry.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Birmingham | Alabama | United States | ||
| 2 | Beverly Hills | California | United States | ||
| 3 | Burbank | California | United States | ||
| 4 | La Jolla | California | United States | ||
| 5 | Los Angeles | California | United States | ||
| 6 | Pomona | California | United States | ||
| 7 | San Diego | California | United States | ||
| 8 | New Haven | Connecticut | United States | ||
| 9 | Fort Myers | Florida | United States | ||
| 10 | Jacksonville | Florida | United States | ||
| 11 | Orange City | Florida | United States | ||
| 12 | Atlanta | Georgia | United States | ||
| 13 | Augusta | Georgia | United States | ||
| 14 | Chicago | Illinois | United States | ||
| 15 | Iowa City | Iowa | United States | ||
| 16 | Louisville | Kentucky | United States | ||
| 17 | New Orleans | Louisiana | United States | ||
| 18 | Baltimore | Maryland | United States | ||
| 19 | Ann Arbor | Michigan | United States | ||
| 20 | Southfield | Michigan | United States | ||
| 21 | Saint Louis | Missouri | United States | ||
| 22 | Hackensack | New Jersey | United States | ||
| 23 | Morristown | New Jersey | United States | ||
| 24 | Somerville | New Jersey | United States | ||
| 25 | New York | New York | United States | ||
| 26 | Durham | North Carolina | United States | ||
| 27 | Hickory | North Carolina | United States | ||
| 28 | Canton | Ohio | United States | ||
| 29 | Cleveland | Ohio | United States | ||
| 30 | Portland | Oregon | United States | ||
| 31 | Danville | Pennsylvania | United States | ||
| 32 | Hershey | Pennsylvania | United States | ||
| 33 | Charleston | South Carolina | United States | ||
| 34 | Nashville | Tennessee | United States | ||
| 35 | Houston | Texas | United States | ||
| 36 | San Antonio | Texas | United States | ||
| 37 | Salt Lake City | Utah | United States | ||
| 38 | Burlington | Vermont | United States |
Sponsors and Collaborators
- Incyte Corporation
Investigators
- Study Director: Peter Langmuir, MD, Incyte Corporation
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT01348490
Other Study ID Numbers:
- INCB18424-258
First Posted:
May 5, 2011
Last Update Posted:
Jan 28, 2020
Last Verified:
Jan 1, 2020
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Incyte Corporation
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | Participants took part in the study at 27 investigative sites in the United States from 15 June 2011 to 19 December 2018. |
|---|---|
| Pre-assignment Detail | A total of 66 participants were enrolled in the study. Fifty-five participants completed 24 weeks of treatment (core treatment period), and 23 participants entered the extension phase. |
| Arm/Group Title | Ruxolitinib 5 Milligram (mg) |
|---|---|
| Arm/Group Description | Doses may not exceed 10 mg bid except in subjects who continue to meet the above dose escalation criteria, and who have, in addition, a PGIC score of minimally worse, much worse or very much worse while receiving 10 mg bid. Such subjects may continue dose escalation to a maximum dose of 15 mg bid. During the extended treatment phase, doses of ruxolitinib may be increased in 5 mg qd increments up to a dose of 25 mg bid if the subject meets the above dose escalation criteria, or per the investigator's discretion. |
| Period Title: Overall Study | |
| STARTED | 66 |
| COMPLETED | 42 |
| NOT COMPLETED | 24 |
Baseline Characteristics
| Arm/Group Title | Ruxolitinib 5 mg |
|---|---|
| Arm/Group Description | Doses may not exceed 10 mg bid except in subjects who continue to meet the above dose escalation criteria, and who have, in addition, a PGIC score of minimally worse, much worse or very much worse while receiving 10 mg bid. Such subjects may continue dose escalation to a maximum dose of 15 mg bid. During the extended treatment phase, doses of ruxolitinib may be increased in 5 mg qd increments up to a dose of 25 mg bid if the subject meets the above dose escalation criteria, or per the investigator's discretion. |
| Overall Participants | 66 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
68.7
(9.44)
|
| Sex: Female, Male (Count of Participants) | |
| Female |
27
40.9%
|
| Male |
39
59.1%
|
| Race/Ethnicity, Customized (Count of Participants) | |
| Hispanic or Latino |
3
4.5%
|
| Non-Hispanic or Non-Latino |
63
95.5%
|
| Race/Ethnicity, Customized (Count of Participants) | |
| White |
58
87.9%
|
| Black or African American |
4
6.1%
|
| Asian |
2
3%
|
| Native Hawaiian or Pacific Islander |
1
1.5%
|
| Other |
1
1.5%
|
Outcome Measures
| Title | Percent Change From Baseline in Spleen Volume at Week 24 by Final Titrated Dose |
|---|---|
| Description | Magnetic resonance imaging (MRI) of the upper and lower abdomen and pelvis was performed to assess spleen volumes. Computed tomography (CT) scan was performed if participant was not a candidate for MRI or if MRI was not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Intent-to-treat (ITT) population included all participants enrolled and treated in the study. |
| Arm/Group Title | 5 mg QD or 5 mg BID | 5 mg AM/ 10 mg PM | 10 mg BID | 10 mg AM/ 15 mg PM or 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants received the final titrated dose of ruxolitinib 5 mg QD or 5 mg BID. | Participants received the final titrated dose of ruxolitinib 5 mg AM plus 10 mg PM. | Participants received the final titrated dose of ruxolitinib 10 mg BID. | Participants received the final titrated dose of ruxolitinib 10 mg AM plus 15 mg PM or 15 mg BID. |
| Measure Participants | 16 | 2 | 27 | 6 |
| Mean (Standard Deviation) [Percentage change from baseline] |
-11.6
(18.68)
|
-17.4
(0.63)
|
-22.4
(22.86)
|
-13.4
(22.29)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 5 mg QD or 5 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | 1-sample t-test with null hypothesis mean >= 0 | |
| Statistical Test of Hypothesis | p-Value | 0.0250 |
| Comments | 1-sample t-test was used. | |
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 5 mg AM/ 10 mg PM |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | 1-sample t-test with null hypothesis mean >= 0 | |
| Statistical Test of Hypothesis | p-Value | 0.0163 |
| Comments | 1-sample t-test was used. | |
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 10 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | 1-sample t-test with null hypothesis mean >= 0 | |
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 1-sample t-test was used. | |
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 4
| Statistical Analysis Overview | Comparison Group Selection | 10 mg AM/ 15 mg PM or 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | 1-sample t-test with null hypothesis mean >= 0 | |
| Statistical Test of Hypothesis | p-Value | 0.2019 |
| Comments | 1-sample t-test was used. | |
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Percent Change From Baseline in Total Symptom Score (TSS) as Measured by the Modified Myelofibrosis Symptom Assessment Form (MFSAF) V2.0 Diary at Week 24 by Final Titrated Dose |
|---|---|
| Description | Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants enrolled and treated in the study. For the 5 mg AM/ 10 mg PM arm, the t-test was not calculated due to only having a single participant. |
| Arm/Group Title | 5 mg QD or 5 mg BID | 5 mg AM/ 10 mg PM | 10 mg BID | 10 mg AM/ 15 mg PM or 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants received the final titrated dose of ruxolitinib 5 mg QD or 5 mg BID. | Participants received the final titrated dose of ruxolitinib 5 mg AM plus 10 mg PM. | Participants received the final titrated dose of ruxolitinib 10 mg BID. | Participants received the final titrated dose of ruxolitinib 10 mg AM plus 15 mg PM or 15 mg BID. |
| Measure Participants | 17 | 1 | 29 | 6 |
| Mean (Standard Deviation) [Percentage change from baseline] |
-6.35
(64.207)
|
-39.51
(NA)
|
-47.54
(46.886)
|
7.95
(113.17)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 5 mg QD or 5 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6887 |
| Comments | 1-sample t-test was used. | |
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | 10 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 1-sample t-test was used. | |
| Method | t-test, 1 sided | |
| Comments | ||
Statistical Analysis 3
| Statistical Analysis Overview | Comparison Group Selection | 10 mg AM/ 15 mg PM or 15 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.8701 |
| Comments | 1-sample t-test was used. | |
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Percentage of Participants With Treatment-emergent Adverse Events (TEAE) |
|---|---|
| Description | TEAE was defined as adverse events that began or worsened from baseline after the first administration of the study drug. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred. |
| Time Frame | Up to Week 156 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety evaluable population included participants who received at least 1 dose of study drug. |
| Arm/Group Title | >0 - 5 mg | >5 - 10 mg | >10 - 15 mg | >15 - 20 mg | >20 mg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ruxolitinib up to 0-5mg. | Participants received ruxolitinib in the range of 6 mg to 10 mg. | Participants received ruxolitinib in the range of 11 to 15 mg. | Participants received ruxolitinib in the range of 16 to 20 mg. | Participants received ruxolitinib, more than 20 mg. |
| Measure Participants | 15 | 66 | 54 | 44 | 9 |
| Number [percentage of participants] |
93.3
141.4%
|
74.2
NaN
|
61.1
NaN
|
77.3
NaN
|
55.6
NaN
|
| Title | Percentage of Participants With New Onset Grade 4 Thrombocytopenia Events as Assessed by Common Terminology Criteria for Adverse Events Version 4.03 (CTCAE V4.03) |
|---|---|
| Description | Participants with platelet count between 50 and 100 × 10^9/L at the screening and/or baseline visit were enrolled in the study. Thrombocytopenia is defined as a condition with low blood platelet count. Grade 4 thrombocytopenia was platelet count < 25 × 10^9/L. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred. |
| Time Frame | Up to Week 156 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety evaluable population included participants who received at least 1 dose of study drug. |
| Arm/Group Title | >0 - 5 mg | >5 - 10 mg | >10 - 15 mg | >15 - 20 mg | >20 mg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ruxolitinib up to 5 mg. | Participants received ruxolitinib in the range of 5 to 10 mg. | Participants received ruxolitinib in the range of 10 to 15 mg. | Participants received ruxolitinib in the range of 15 to 20 mg. | Participants received ruxolitinib, more than 20 mg. |
| Measure Participants | 13 | 66 | 53 | 43 | 8 |
| Number [percentage of participants] |
23.1
35%
|
3.0
NaN
|
5.7
NaN
|
4.7
NaN
|
0.0
NaN
|
| Title | Percentage of Participants With New Onset Grade 2 or Higher Hemorrhage as Assessed by CTCAE V4.03 |
|---|---|
| Description | Hemorrhages were defined as any lower level terms by MedDRA included in the Standardized MedDRA Query (SMQ) for hemorrhage terms. Participants were analyzed based on the number of subjects who received a dose within the dose group. The percentages for each column are calculated using this N. Participants who had more than 1 event in an AE category (eg, treatment-related TEAE) are counted once at each dose level the event occurred. |
| Time Frame | Up to Week 156 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Safety evaluable population included participants who received at least 1 dose of study drug. |
| Arm/Group Title | >0 - 5 mg | >5 - 10 mg | >10 - 15 mg | >15 - 20 mg | >20 mg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received ruxolitinib up to 5 mg. | Participants received ruxolitinib in the range of 5 to 10 mg. | Participants received ruxolitinib in the range of 10 to 15 mg. | Participants received ruxolitinib in the range of 15 to 20 mg. | Participants received ruxolitinib, more than 20 mg. |
| Measure Participants | 15 | 66 | 54 | 44 | 9 |
| Number [percentage of participants] |
6.7
10.2%
|
3.0
NaN
|
1.9
NaN
|
2.3
NaN
|
11.1
NaN
|
| Title | Percent Change in Spleen Volume at Week 24 Compared to Baseline |
|---|---|
| Description | MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant was not a candidate for MRI, or if MRI was not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants enrolled and treated in the study. |
| Arm/Group Title | Ruxolitinib |
|---|---|
| Arm/Group Description | Participants who received ruxolitinib doses as 5 mg QD or 5 mg BID, 5 mg AM/ 10 mg PM, 10 mg BID, and 10 mg AM/ 15 mg PM or 15 mg BID. |
| Measure Participants | 51 |
| Mean (Standard Deviation) [Percentage] |
-17.8
(21.27)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 5 mg QD or 5 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.0001 |
| Comments | 1-sample t-test was used. | |
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Percent Change in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline |
|---|---|
| Description | Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms.. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| ITT population included all participants enrolled and treated in the study. |
| Arm/Group Title | Ruxolitinib |
|---|---|
| Arm/Group Description | Participants who received ruxolitinib doses as 5 mg QD or 5 mg BID, 5 mg AM/ 10 mg PM, 10 mg BID, and 10 mg AM/ 15 mg PM or 15 mg BID. |
| Measure Participants | 53 |
| Mean (Standard Deviation) [Percentage change from baseline] |
-27.90
(64.818)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 5 mg QD or 5 mg BID |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0028 |
| Comments | 1-sample t-test was used. | |
| Method | t-test, 1 sided | |
| Comments | ||
| Title | Percentage of Participants With ≥ 35% Reduction in Spleen Volume at Week 24 Compared to Baseline |
|---|---|
| Description | MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant is not a candidate for MRI, or if MRI is not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy evaluable participants included all participants enrolled and treated in the study. |
| Arm/Group Title | 5 mg QD or 5 mg BID | 5 mg AM/ 10 mg PM | 10 mg BID | 10 mg AM/ 15 mg PM or 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants received the final titrated dose of ruxolitinib 5 mg QD or 5 mg BID. | Participants received the final titrated dose of ruxolitinib 5 mg AM plus 10 mg PM. | Participants received the final titrated dose of ruxolitinib 10 mg BID. | Participants received the final titrated dose of ruxolitinib 10 mg AM plus 15 mg PM or 15 mg BID. |
| Measure Participants | 21 | 3 | 33 | 7 |
| Number (95% Confidence Interval) [percentage of participants] |
4.8
7.3%
|
0.0
NaN
|
24.2
NaN
|
28.6
NaN
|
| Title | Percentage of Participants With ≥10% Reduction in Spleen Volume at Week 24 Compared to Baseline |
|---|---|
| Description | MRI of the upper and lower abdomen and pelvis was performed, to assess spleen volumes. CT scan was performed if participant is not a candidate for MRI, or if MRI is not readily available. MRI was performed with a body coil. Spleen volume was obtained by outlining the circumference of the organ and determining the volume using the validated technique of least squares. The MRI (or CT scan in applicable participants) was performed on the first or second day of the baseline period (ie, Day -7 or Day -6), and the site radiologist sent the scan to the central imaging laboratory that same day. The CT scans were processed by the same central laboratory used for MRIs. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy evaluable participants included all participants enrolled and treated in the study. |
| Arm/Group Title | 5 mg QD or 5 mg BID | 5 mg AM/ 10 mg PM | 10 mg BID | 10 mg AM/ 15 mg PM or 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants received the final titrated dose of ruxolitinib 5 mg QD or 5 mg BID. | Participants received the final titrated dose of ruxolitinib 5 mg AM plus 10 mg PM. | Participants received the final titrated dose of ruxolitinib 10 mg BID. | Participants received the final titrated dose of ruxolitinib 10 mg AM plus 15 mg PM or 15 mg BID. |
| Measure Participants | 21 | 3 | 33 | 7 |
| Number (95% Confidence Interval) [percentage of participants] |
42.9
65%
|
66.7
NaN
|
63.6
NaN
|
28.6
NaN
|
| Title | Percentage of Participants With ≥ 50% Improvement in Total Symptom Score as Measured by the Modified MFSAF V2.0 Diary at Week 24 Compared to Baseline |
|---|---|
| Description | Symptoms of myelofibrosis were assessed using a modified Myelofibrosis Symptom Assessment Form (MFSAF) Version 2.0 diary. Using the diary, patients rated the following symptoms on a scale from 0 (absent) to 10 (worst imaginable): night sweats, itching, abdominal discomfort, pain under ribs on left, feeling of fullness (early satiety), and muscle/bone pain. The total symptom score ranged from 0-60 and was calculated as the sum of the 6 symptom scores. A higher score indicates worse symptoms. |
| Time Frame | Baseline and Week 24 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy evaluable participants included all participants enrolled and treated in the study. |
| Arm/Group Title | 5 mg QD or 5 mg BID | 5 mg AM/ 10 mg PM | 10 mg BID | 10 mg AM/ 15 mg PM or 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants received the final titrated dose of ruxolitinib 5 mg QD or 5 mg BID. | Participants received the final titrated dose of ruxolitinib 5 mg AM plus 10 mg PM. | Participants received the final titrated dose of ruxolitinib 10 mg BID. | Participants received the final titrated dose of ruxolitinib 10 mg AM plus 15 mg PM or 15 mg BID. |
| Measure Participants | 21 | 3 | 34 | 7 |
| Number (95% Confidence Interval) [percentage of participants] |
28.6
43.3%
|
0.0
NaN
|
44.1
NaN
|
28.6
NaN
|
| Title | Change in Spleen Length Measured by Palpation |
|---|---|
| Description | Measurement of spleen length below the left costal margin was measured by palpation at each study visit. Investigators were provided with a soft centimeter ruler so that palpable spleen length was measured in centimeters and not in finger breadths. 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 | Up to Week 156 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy evaluable participants included all participants enrolled and treated in the study. 'Number Analyzed' is number of participants with data available at a particular time point. |
| Arm/Group Title | 5 mg QD or 5 mg BID | 5 mg AM/ 10 mg PM | 10 mg BID | 10 mg AM/ 15 mg PM or 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants received the final titrated dose of ruxolitinib 5 mg QD or 5 mg BID. | Participants received the final titrated dose of ruxolitinib 5 mg AM plus 10 mg PM. | Participants received the final titrated dose of ruxolitinib 10 mg BID. | Participants received the final titrated dose of ruxolitinib 10 mg AM plus 15 mg PM or 15 mg BID. |
| Measure Participants | 21 | 4 | 34 | 7 |
| Baseline |
11.48
(5.810)
|
14.00
(4.359)
|
13.13
(8.241)
|
14.71
(6.726)
|
| Change at Week 4 |
-3.40
(3.068)
|
-4.00
(6.083)
|
-1.84
(3.195)
|
0.00
(3.688)
|
| Change at Week 8 |
-4.65
(3.558)
|
-5.33
(4.933)
|
-2.81
(3.514)
|
-1.14
(2.340)
|
| Change at Week 12 |
-4.53
(4.812)
|
-6.50
(3.536)
|
-3.74
(5.118)
|
-3.71
(7.544)
|
| Change at Week 16 |
-3.79
(4.973)
|
-4.50
(3.536)
|
-3.69
(4.343)
|
-2.00
(2.449)
|
| Change at Week 20 |
-4.56
(4.844)
|
-7.50
(4.950)
|
-5.28
(5.567)
|
-3.50
(7.064)
|
| Change at Week 24 |
-4.25
(5.092)
|
-7.00
(5.657)
|
-4.57
(5.541)
|
-1.33
(3.983)
|
| Change at Week 36 |
-7.00
(NA)
|
-11.00
(NA)
|
-2.75
(3.862)
|
1.00
(NA)
|
| Change at Week 48 |
-7.00
(NA)
|
-11.00
(NA)
|
-2.33
(2.517)
|
0.00
(0.000)
|
| Change at Week 60 |
-7.00
(NA)
|
-11.00
(NA)
|
-2.67
(2.517)
|
1.50
(2.121)
|
| Change at Week 72 |
-4.00
(NA)
|
-11.00
(NA)
|
-1.50
(2.121)
|
1.00
(NA)
|
| Change at Week 84 |
-4.00
(NA)
|
-3.00
(NA)
|
-2.00
(NA)
|
|
| Change at Week 96 |
-4.00
(NA)
|
-8.00
(NA)
|
0.00
(NA)
|
|
| Change at Week 108 |
-4.00
(NA)
|
-10.00
(NA)
|
0.00
(NA)
|
|
| Change at Week 120 |
-4.00
(NA)
|
-6.00
(NA)
|
2.00
(NA)
|
|
| Change at Week 132 |
-4.00
(NA)
|
-5.00
(NA)
|
1.00
(NA)
|
|
| Change at Week 144 |
-4.00
(NA)
|
-3.00
(NA)
|
0.00
(NA)
|
|
| Change at Week 156 |
-4.00
(NA)
|
-3.00
(NA)
|
0.00
(NA)
|
| Title | Percent Change From Baseline in Spleen Length Measured by Palpation |
|---|---|
| Description | Measurement of spleen length below the left costal margin was measured by palpation at each study visit. Investigators were provided with a soft centimeter ruler so that palpable spleen length was measured in centimeters and not in finger breadths. 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 | Up to Week 156 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy evaluable participants included all participants enrolled and treated in the study. 'Number Analyzed' is number of participants with data available at a particular time point. |
| Arm/Group Title | 5 mg QD or 5 mg BID | 5 mg AM/ 10 mg PM | 10 mg BID | 10 mg AM/ 15 mg PM or 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants received the final titrated dose of ruxolitinib 5 mg QD or 5 mg BID. | Participants received the final titrated dose of ruxolitinib 5 mg AM plus 10 mg PM. | Participants received the final titrated dose of ruxolitinib 10 mg BID. | Participants received the final titrated dose of ruxolitinib 10 mg AM plus 15 mg PM or 15 mg BID. |
| Measure Participants | 21 | 4 | 34 | 7 |
| Percent Change at Week 4 |
-38.61
(36.532)
|
-26.62
(36.906)
|
-21.88
(33.800)
|
-1.42
(22.902)
|
| Percent Change at Week 8 |
-50.64
(39.930)
|
-37.95
(28.772)
|
-28.32
(31.151)
|
-8.72
(13.991)
|
| Percent Change at Week 12 |
-49.90
(48.623)
|
-50.35
(8.348)
|
-38.21
(39.936)
|
-22.41
(40.833)
|
| Percent Change at Week 16 |
-43.24
(48.173)
|
-32.99
(15.222)
|
-38.67
(36.070)
|
-14.33
(14.903)
|
| Percent Change at Week 20 |
-44.58
(46.490)
|
-56.60
(17.187)
|
-48.06
(38.826)
|
-27.75
(39.024)
|
| Percent Change at Week 24 |
-45.39
(53.913)
|
-51.04
(25.043)
|
-42.01
(36.899)
|
-9.89
(25.001)
|
| Percent Change at Week 36 |
-58.33
(NA)
|
-68.75
(NA)
|
-20.76
(27.637)
|
5.00
(NA)
|
| Percent Change at Week 48 |
-58.33
(NA)
|
-68.75
(NA)
|
-31.82
(19.285)
|
0.00
(NA)
|
| Percent Change at Week 60 |
-58.33
(NA)
|
-68.75
(NA)
|
-36.36
(12.856)
|
15.00
(NA)
|
| Percent Change at Week 72 |
-33.33
(NA)
|
-68.75
(NA)
|
-27.27
(NA)
|
5.00
(NA)
|
| Percent Change at Week 84 |
-33.33
(NA)
|
-27.27
(NA)
|
-10.00
(NA)
|
|
| Percent Change at Week 96 |
-33.33
(NA)
|
-50.00
(NA)
|
||
| Percent Change at Week 108 |
-33.33
(NA)
|
-62.50
(NA)
|
||
| Percent Change at Week 120 |
-33.33
(NA)
|
-37.50
(NA)
|
||
| Percent Change at Week 132 |
-33.33
(NA)
|
-31.25
(NA)
|
||
| Percent Change at Week 144 |
-33.33
(NA)
|
-18.75
(NA)
|
||
| Percent Change at Week 156 |
-33.33
(NA)
|
-18.75
(NA)
|
| Title | Patient Global Impression of Change (PGIC) Score at Each Visit |
|---|---|
| Description | Symptoms of myelofibrosis were assessed using the PGIC questionnaire. Using the questionnaire, patients rated the overall sense of treatment effect on their symptoms on a scale of 1 (very much improved)- 7(very much worse). The specific wording was: Since the start of the treatment you've received in this study, your myelofibrosis symptoms are: 1) Very much improved, 2) Much improved, 3) Minimally improved, 4) No change, 5) Minimally worse, 6) Much worse, 7) Very much worse. A higher score indicates worse symptoms. |
| Time Frame | Up to Week 156 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Efficacy evaluable participants included all participants enrolled and treated in the study. 'Number Analyzed' is number of participants with data available at the particular time point. |
| Arm/Group Title | 5 mg QD or 5 mg BID | 5 mg AM/ 10 mg PM | 10 mg BID | 10 mg AM/ 15 mg PM or 15 mg BID |
|---|---|---|---|---|
| Arm/Group Description | Participants received the final titrated dose of ruxolitinib 5 mg QD or 5 mg BID. | Participants received the final titrated dose of ruxolitinib 5 mg AM plus 10 mg PM. | Participants received the final titrated dose of ruxolitinib 10 mg BID. | Participants received the final titrated dose of ruxolitinib 10 mg AM plus 15 mg PM or 15 mg BID. |
| Measure Participants | 21 | 4 | 34 | 7 |
| Week 4 |
2.8
(0.89)
|
2.8
(1.26)
|
2.6
(1.09)
|
3.3
(0.76)
|
| Week 8 |
2.7
(1.22)
|
2.3
(0.96)
|
2.2
(0.99)
|
2.9
(0.69)
|
| Week 12 |
2.4
(0.96)
|
2.3
(1.15)
|
2.2
(1.17)
|
3.4
(1.27)
|
| Week 16 |
2.4
(0.83)
|
2.0
(1.00)
|
1.9
(0.91)
|
3.3
(0.95)
|
| Week 20 |
2.4
(0.86)
|
2.3
(0.58)
|
1.9
(1.11)
|
2.3
(0.82)
|
| Week 24 |
2.9
(1.27)
|
2.3
(0.58)
|
1.9
(0.98)
|
2.0
(1.00)
|
| Week 36 |
2.0
(NA)
|
3.0
(NA)
|
1.8
(0.50)
|
2.5
(0.71)
|
| Week 48 |
2.5
(0.71)
|
1.3
(0.58)
|
2.0
(0.00)
|
|
| Week 60 |
2.0
(NA)
|
2.5
(0.71)
|
1.7
(0.58)
|
3.0
(0.00)
|
| Week 72 |
2.0
(NA)
|
2.5
(0.71)
|
4.0
(NA)
|
|
| Week 84 |
2.0
(NA)
|
1.0
(0.00)
|
3.0
(NA)
|
|
| Week 96 |
2.0
(NA)
|
2.5
(0.71)
|
||
| Week 108 |
2.0
(NA)
|
2.5
(0.71)
|
1.0
(NA)
|
|
| Week 120 |
2.0
(NA)
|
2.5
(0.71)
|
||
| Week 132 |
2.0
(NA)
|
3.0
(1.41)
|
1.0
(NA)
|
|
| Week 144 |
2.0
(NA)
|
2.5
(0.71)
|
1.0
(NA)
|
|
| Week 156 |
2.0
(NA)
|
3.0
(1.41)
|
1.0
(NA)
|
Adverse Events
| Time Frame | Up to approximately 161 weeks | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety evaluable population included participants who received at least 1 dose of study drug. Data for adverse events was reported as per the total daily dose the participant was receiving at the time of the event. | |||||||||
| Arm/Group Title | >0 - 5 mg | >5 - 10 mg | >10 - 15 mg | >15 - 20 mg | >20 mg | |||||
| Arm/Group Description | Participants received ruxolitinib up to 5 mg. | Participants received ruxolitinib in the range of 5 to 10 mg. | Participants received ruxolitinib in the range of 10 to 15 mg. | Participants received ruxolitinib in the range of 15 to 20 mg. | Participants received ruxolitinib, more than 20 mg. | |||||
All Cause Mortality |
||||||||||
| >0 - 5 mg | >5 - 10 mg | >10 - 15 mg | >15 - 20 mg | >20 mg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 2/44 (4.5%) | 0/9 (0%) | |||||
Serious Adverse Events |
||||||||||
| >0 - 5 mg | >5 - 10 mg | >10 - 15 mg | >15 - 20 mg | >20 mg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/15 (33.3%) | 8/66 (12.1%) | 4/54 (7.4%) | 9/44 (20.5%) | 1/9 (11.1%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 0/15 (0%) | 0/66 (0%) | 1/54 (1.9%) | 2/44 (4.5%) | 0/9 (0%) | |||||
| Leukocytosis | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Thrombocytopenia | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Bradycardia | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Cardiac failure congestive | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal pain | 1/15 (6.7%) | 0/66 (0%) | 1/54 (1.9%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Colitis | 0/15 (0%) | 1/66 (1.5%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Nausea | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Rectal haemorrhage | 0/15 (0%) | 1/66 (1.5%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Retroperitoneal haemorrhage | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Vomiting | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| General disorders | ||||||||||
| Death | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Hepatobiliary disorders | ||||||||||
| Cholelithiasis | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Infections and infestations | ||||||||||
| Cellulitis | 0/15 (0%) | 0/66 (0%) | 1/54 (1.9%) | 0/44 (0%) | 0/9 (0%) | |||||
| Gastroenteritis | 0/15 (0%) | 1/66 (1.5%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Pneumonia | 1/15 (6.7%) | 1/66 (1.5%) | 0/54 (0%) | 1/44 (2.3%) | 1/9 (11.1%) | |||||
| Viral infection | 0/15 (0%) | 1/66 (1.5%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Subdural haematoma | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Tumour lysis syndrome | 0/15 (0%) | 0/66 (0%) | 1/54 (1.9%) | 0/44 (0%) | 0/9 (0%) | |||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Lung adenocarcinoma metastatic | 0/15 (0%) | 1/66 (1.5%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Squamous cell carcinoma | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Nervous system disorders | ||||||||||
| Cerebrovascular accident | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Dizziness | 1/15 (6.7%) | 1/66 (1.5%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Psychiatric disorders | ||||||||||
| Hypnagogic hallucination | 0/15 (0%) | 1/66 (1.5%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Reproductive system and breast disorders | ||||||||||
| Epididymitis | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Chronic obstructive pulmonary disease | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Dyspnoea | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Hypoxia | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Pneumonitis | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Vascular disorders | ||||||||||
| Haematoma | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| >0 - 5 mg | >5 - 10 mg | >10 - 15 mg | >15 - 20 mg | >20 mg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 13/15 (86.7%) | 43/66 (65.2%) | 26/54 (48.1%) | 31/44 (70.5%) | 5/9 (55.6%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 3/15 (20%) | 7/66 (10.6%) | 4/54 (7.4%) | 5/44 (11.4%) | 0/9 (0%) | |||||
| Reticulocytosis | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Splenomegaly | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Thrombocytopenia | 3/15 (20%) | 11/66 (16.7%) | 4/54 (7.4%) | 2/44 (4.5%) | 1/9 (11.1%) | |||||
| Cardiac disorders | ||||||||||
| Cardiomegaly | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Cyanosis | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Tachycardia | 0/15 (0%) | 4/66 (6.1%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Ear pain | 1/15 (6.7%) | 1/66 (1.5%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Eye disorders | ||||||||||
| Scleral haemorrhage | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Visual impairment | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 1/9 (11.1%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal distension | 0/15 (0%) | 0/66 (0%) | 3/54 (5.6%) | 2/44 (4.5%) | 1/9 (11.1%) | |||||
| Abdominal pain | 2/15 (13.3%) | 4/66 (6.1%) | 2/54 (3.7%) | 2/44 (4.5%) | 1/9 (11.1%) | |||||
| Abdominal pain upper | 1/15 (6.7%) | 1/66 (1.5%) | 1/54 (1.9%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Diarrhoea | 1/15 (6.7%) | 7/66 (10.6%) | 7/54 (13%) | 3/44 (6.8%) | 1/9 (11.1%) | |||||
| Gastrooesophageal reflux disease | 0/15 (0%) | 1/66 (1.5%) | 0/54 (0%) | 0/44 (0%) | 1/9 (11.1%) | |||||
| Nausea | 2/15 (13.3%) | 6/66 (9.1%) | 2/54 (3.7%) | 4/44 (9.1%) | 0/9 (0%) | |||||
| Vomiting | 2/15 (13.3%) | 3/66 (4.5%) | 0/54 (0%) | 3/44 (6.8%) | 0/9 (0%) | |||||
| General disorders | ||||||||||
| Asthenia | 0/15 (0%) | 0/66 (0%) | 4/54 (7.4%) | 0/44 (0%) | 0/9 (0%) | |||||
| Chest discomfort | 0/15 (0%) | 0/66 (0%) | 1/54 (1.9%) | 0/44 (0%) | 1/9 (11.1%) | |||||
| Early satiety | 0/15 (0%) | 2/66 (3%) | 0/54 (0%) | 0/44 (0%) | 1/9 (11.1%) | |||||
| Fatigue | 2/15 (13.3%) | 7/66 (10.6%) | 5/54 (9.3%) | 3/44 (6.8%) | 1/9 (11.1%) | |||||
| Oedema | 1/15 (6.7%) | 2/66 (3%) | 1/54 (1.9%) | 0/44 (0%) | 0/9 (0%) | |||||
| Oedema peripheral | 1/15 (6.7%) | 9/66 (13.6%) | 4/54 (7.4%) | 6/44 (13.6%) | 0/9 (0%) | |||||
| Pain | 1/15 (6.7%) | 1/66 (1.5%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Pyrexia | 1/15 (6.7%) | 0/66 (0%) | 3/54 (5.6%) | 3/44 (6.8%) | 1/9 (11.1%) | |||||
| Hepatobiliary disorders | ||||||||||
| Cholelithiasis | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Gallbladder disorder | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Immune system disorders | ||||||||||
| Seasonal allergy | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 1/9 (11.1%) | |||||
| Infections and infestations | ||||||||||
| Herpes simplex | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 1/9 (11.1%) | |||||
| Oral herpes | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Sinusitis | 1/15 (6.7%) | 1/66 (1.5%) | 1/54 (1.9%) | 1/44 (2.3%) | 1/9 (11.1%) | |||||
| Upper respiratory tract infection | 1/15 (6.7%) | 3/66 (4.5%) | 2/54 (3.7%) | 6/44 (13.6%) | 1/9 (11.1%) | |||||
| Vaginal infection | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Contusion | 0/15 (0%) | 5/66 (7.6%) | 3/54 (5.6%) | 2/44 (4.5%) | 0/9 (0%) | |||||
| Transfusion reaction | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Investigations | ||||||||||
| Blast cell count increased | 1/15 (6.7%) | 1/66 (1.5%) | 1/54 (1.9%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Blood bilirubin increased | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Blood creatinine decreased | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Cardioactive drug level increased | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Electrocardiogram QT prolonged | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Haemoglobin decreased | 1/15 (6.7%) | 0/66 (0%) | 1/54 (1.9%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Neutrophil count decreased | 0/15 (0%) | 1/66 (1.5%) | 0/54 (0%) | 3/44 (6.8%) | 0/9 (0%) | |||||
| Occult blood positive | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 1/9 (11.1%) | |||||
| Platelet count decreased | 0/15 (0%) | 3/66 (4.5%) | 3/54 (5.6%) | 3/44 (6.8%) | 0/9 (0%) | |||||
| Serum ferritin increased | 1/15 (6.7%) | 1/66 (1.5%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| White blood cell count decreased | 1/15 (6.7%) | 1/66 (1.5%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| White blood cell count increased | 1/15 (6.7%) | 1/66 (1.5%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 2/15 (13.3%) | 0/66 (0%) | 1/54 (1.9%) | 2/44 (4.5%) | 0/9 (0%) | |||||
| Hyperkalaemia | 0/15 (0%) | 2/66 (3%) | 1/54 (1.9%) | 2/44 (4.5%) | 1/9 (11.1%) | |||||
| Hypermagnesaemia | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Hyperuricaemia | 1/15 (6.7%) | 3/66 (4.5%) | 1/54 (1.9%) | 3/44 (6.8%) | 0/9 (0%) | |||||
| Hypocalcaemia | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Iron overload | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 1/9 (11.1%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Arthralgia | 0/15 (0%) | 4/66 (6.1%) | 1/54 (1.9%) | 2/44 (4.5%) | 1/9 (11.1%) | |||||
| Back pain | 0/15 (0%) | 0/66 (0%) | 3/54 (5.6%) | 0/44 (0%) | 0/9 (0%) | |||||
| Bone pain | 0/15 (0%) | 1/66 (1.5%) | 1/54 (1.9%) | 1/44 (2.3%) | 1/9 (11.1%) | |||||
| Muscle spasms | 1/15 (6.7%) | 2/66 (3%) | 1/54 (1.9%) | 2/44 (4.5%) | 0/9 (0%) | |||||
| Musculoskeletal pain | 1/15 (6.7%) | 2/66 (3%) | 1/54 (1.9%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Pain in extremity | 1/15 (6.7%) | 1/66 (1.5%) | 1/54 (1.9%) | 0/44 (0%) | 0/9 (0%) | |||||
| Nervous system disorders | ||||||||||
| Dizziness | 0/15 (0%) | 3/66 (4.5%) | 0/54 (0%) | 3/44 (6.8%) | 1/9 (11.1%) | |||||
| Headache | 0/15 (0%) | 4/66 (6.1%) | 3/54 (5.6%) | 2/44 (4.5%) | 1/9 (11.1%) | |||||
| Presyncope | 0/15 (0%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 1/9 (11.1%) | |||||
| Psychiatric disorders | ||||||||||
| Depression | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Mental status changes | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Renal and urinary disorders | ||||||||||
| Urine flow decreased | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 1/15 (6.7%) | 3/66 (4.5%) | 2/54 (3.7%) | 0/44 (0%) | 0/9 (0%) | |||||
| Dyspnoea | 1/15 (6.7%) | 0/66 (0%) | 1/54 (1.9%) | 0/44 (0%) | 0/9 (0%) | |||||
| Dyspnoea exertional | 0/15 (0%) | 1/66 (1.5%) | 0/54 (0%) | 0/44 (0%) | 2/9 (22.2%) | |||||
| Epistaxis | 2/15 (13.3%) | 0/66 (0%) | 2/54 (3.7%) | 2/44 (4.5%) | 1/9 (11.1%) | |||||
| Nasal congestion | 1/15 (6.7%) | 1/66 (1.5%) | 0/54 (0%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Pleural effusion | 2/15 (13.3%) | 1/66 (1.5%) | 2/54 (3.7%) | 1/44 (2.3%) | 0/9 (0%) | |||||
| Productive cough | 1/15 (6.7%) | 0/66 (0%) | 1/54 (1.9%) | 0/44 (0%) | 0/9 (0%) | |||||
| Pulmonary hypertension | 1/15 (6.7%) | 0/66 (0%) | 0/54 (0%) | 0/44 (0%) | 0/9 (0%) | |||||
| Sinus congestion | 0/15 (0%) | 1/66 (1.5%) | 0/54 (0%) | 1/44 (2.3%) | 1/9 (11.1%) | |||||
| Upper-airway cough syndrome | 1/15 (6.7%) | 1/66 (1.5%) | 1/54 (1.9%) | 0/44 (0%) | 0/9 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Ecchymosis | 1/15 (6.7%) | 2/66 (3%) | 0/54 (0%) | 1/44 (2.3%) | 1/9 (11.1%) | |||||
| Night sweats | 0/15 (0%) | 4/66 (6.1%) | 0/54 (0%) | 2/44 (4.5%) | 2/9 (22.2%) | |||||
| Vascular disorders | ||||||||||
| Hypertension | 1/15 (6.7%) | 2/66 (3%) | 0/54 (0%) | 2/44 (4.5%) | 1/9 (11.1%) | |||||
Limitations/Caveats
Participants with platelet counts of 50 to 100 x 10^9/L were enrolled to begin ruxolitinib at 5 mg BID. Subjects could then titrate their dose to an dose that offers benefit. Only the overall data was calculated for the Participant and Baseline data.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Clinical Study Agreement
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Incyte Corporation |
| Phone | 1-855-463-3463 |
| medinfo@incyte.com |
Responsible Party:
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT01348490
Other Study ID Numbers:
- INCB18424-258
First Posted:
May 5, 2011
Last Update Posted:
Jan 28, 2020
Last Verified:
Jan 1, 2020