Controlled Myelofibrosis Study With Oral Janus-associated Kinase (JAK) Inhibitor Treatment-II: The COMFORT-II Trial

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00934544
• Collaborator: (none)
• Enrollment: 219
• Locations: 61
• Arms: 2
• Actual Duration (Months): 68.1
• Patients Per Site: 3.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This was an open label, randomized study comparing the efficacy and safety of randomized 2:1 Ruxolitinib tablets versus best-available therapy, as selected by the investigator. The purpose was to compare the efficacy, safety and tolerability of Ruxolitinib (INC424/INCB018424) given twice daily to the best-available therapy, in subjects with primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV-MF) or post essential thrombocythemia myelofibrosis (PET-MF).

Condition or Disease	Intervention/Treatment	Phase
Myelofibrosis	Drug: Ruxolitinib; Drug: Best Available Therapy (BAT)	Phase 3

Detailed Description

This study included a randomized treatment phase, followed by an extension phase. The treatment phase lasted from Study Day 1 (day of randomization) to the occurrence of a protocol-specified progressive disease event or study conclusion, whichever came first. The extension phase (including crossover of control group patients) lasted from the progressive disease event until the earliest of the following events: a) the patient was no longer receiving clinical benefit, b) the patient chose to withdraw from the study, or c) the study ended. All patients received ruxolitinib in the extension phase of the study. Maximum individual patient duration was 5 years.

Study Design

• Study Type: Interventional
• Actual Enrollment: 219 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Randomized Study of Ruxolitinib Tablets Compared to Best Available Therapy in Subjects With Primary Myelofibrosis, Post-Polycythemia Vera-Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis
• Actual Study Start Date: Jul 1, 2009
• Actual Primary Completion Date: Mar 4, 2015
• Actual Study Completion Date: Mar 4, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ruxolitinib 5 mg tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule	Drug: Ruxolitinib; 5 mg tablets packaged as 60-count in high-density polyethylene bottles
Active Comparator: Best Available Therapy (BAT) Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment. Patients randomized to BAT were eligible to cross over to receive open-label ruxolitinib after a qualifying progression event, if they met the safety criteria. After the primary analysis in January 2011, patients randomized to receive BAT were allowed to cross over to receive ruxolitinib and move to the extension phase of the study without a qualifying progression event.	Drug: Best Available Therapy (BAT); Prescribing and usage per respective package inserts

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 48 [Baseline, Week 48]

   The change in spleen volume from baseline to week 48 was measured by magnetic resonance imaging (MRI) (or by computer tomography (CT) for participants unable to undergo MRI) and was calculated only for participants who had an evaluable spleen volume at baseline. The percentage of participants achieving a greater than or equal to 35% reduction in spleen volume from baseline to week 48 was then calculated by treatment group.

Secondary Outcome Measures

1. Duration of Maintenance of Spleen Volume Reduction (Median) [Baseline, up to Year 5]

   DoMSR is defined as the interval between the first spleen volume measurement that is >=35% reduction from baseline and the first scan that is no longer = 35% reduction AND that is a >25% increase over nadir. It was evaluated using the Kaplan-Meier estimate for each treatment arm. The analysis was performed only for subjects who achieved greater than 35% reduction in spleen volume.

2. Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates) [Baseline, up to Year 5]

   This is defined as the interval between randomization and date of the first MRI showing a 35% reduction from baseline in spleen volume. The analysis was performed for participants who achieved a 35% reduction in spleen volume.

3. Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24 [Baseline, Week 24]

   The change in spleen volume from baseline to week 24 was measured by magnetic resonance imaging (MRI) (or by computer tomography (CT) for participants unable to undergo MRI) and was calculated only for participants who had an evaluable spleen volume at baseline. The percentage of participants achieving a greater than or equal to 35% reduction in spleen volume from baseline to week 24 was then calculated by treatment group.

4. Time to First at Least 35% Reduction in Spleen Volume From Baseline by Treatment (Primary Analysis) [Time from randomization and date of the first MRI showing at least 35% reduction from baseline in spleen volume]

   This is defined as the interval between randomization and date of the first MRI showing at least 35% reduction from baseline in spleen volume. The analysis was performed for participants who achieved a 35% reduction in spleen volume

5. Progression-free Survival (PFS) [Time from randomization and the earliest of either increase in spleen volume >=25% from on-study nadir, splenic irradiation, splenectomy, leukemic transformation or death]

   Median of time progression free survival (95% CI), years

6. Leukemia-free Survival (LFS) [Time from randomization and earliest of either leukemia or death]

   Time from randomization and earliest of either (1) date of bone marrow blast count of 20% or greater; (2) date of first peripheral blast count of 20% or greater that was subsequently confirmed to sustain for at least 8 weeks; (3) date of death from any cause

7. Overall Survival (OS) [From randomization until death from any cause]

   Defined as the interval between randomization and the date of the bone marrow blast count of 20% or greater OR the date of the first peripheral blast count of 20% or greater that was subsequently confirmed to have been sustained for at least 8 weeks OR the date of death from any cause, whichever occurs first. OS was summarized using Kaplan-Meier estimates for each treatment arm. The estimates were supplemented by tables of number of events and probability estimates at several timepoints

8. Percentage of Participants With Bone Marrow Histomorphology at Week 48 (Primary Analysis) [48 weeks]

   This was noted as fibrosis density and was tabulated by fibrosis grade at baseline and at week 48 (post-baseline). Descriptive statistics (participant percentages) were used. Fibrosis grades: 0 Scattered linear reticulin with no intersections corresponding to normal bone marrow ; 1 Loose network of reticulin with many intersections, especially in perivascular areas; 2 Diffuse and dense increase in reticulin with extensive intersections, occasionally with only focal bundles of collagen and/or focal osteosclerosis; 3 Diffuse and dense increase in reticulin with extensive intersections with coarse bundles of collagen, often associated with significant osteosclerosis

9. Bone Marrow Histomorphology [Baseline, once a year]

   Shift table from baseline to last available postbaseline fibrosis grade by treatment The grade gives an indication of the activity or amount of inflammation and the stage represents the amount of fibrosis or scarring. The grade is assigned a number based on the degree of inflammation, which is usually scored from 0-4 with 0 being no activity and 3 or 4 considered severe activity

10. Duration of Follow-up by Treatment [baseline, 260 weeks (end of study)]

    Number of Participants with duration of Follow up

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects must be diagnosed with PMF, PPV-MF or PET-MF according to the 2008 World Health Organization criteria

• Subjects with MF requiring therapy must be classified as high risk OR intermediate risk level 2 according to the prognostic factors defined by the International Working Group

• Subjects with an ECOG performance status of 0, 1, 2 or 3

• Subjects with peripheral blood blast count of < 10%.

• Subjects who have not previously received treatment with a JAK inhibitor

Exclusion Criteria:

• Subjects with a life expectancy of less than 6 months

• Subjects with inadequate bone marrow reserve as demonstrated by specific clinical laboratory counts

• Subjects with any history of platelet counts < 50,000/µL or ANC < 500/µL except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason

• Subjects with inadequate liver or renal function

• Subjects with clinically significant bacterial, fungal, parasitic or viral infection which require therapy

• Subjects with an active malignancy over the previous 5 years except specific skin cancers

• Subjects with severe cardiac conditions

• Subjects who have had splenic irradiation within 12 months

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Innsbruck		Austria	6020
2	Novartis Investigative Site	Linz		Austria	4010
3	Novartis Investigative Site	Salzburg		Austria	5020
4	Novartis Investigative Site	Vienna		Austria	A-1090
5	Novartis Investigative Site	Antwerp		Belgium	2020
6	Novartis Investigative Site	Antwerp		Belgium	2060
7	Novartis Investigative Site	Brugge		Belgium	8000
8	Novartis Investigative Site	Brussel		Belgium	1200
9	Novartis Investigative Site	Hasselt		Belgium	3500
10	Novartis Investigative Site	Kortrijk		Belgium	8500
11	Novartis Investigative Site	La Louvière		Belgium	7100
12	Novartis Investigative Site	Leuven		Belgium	3000
13	Novartis Investigative Site	Roeselare		Belgium	8800
14	Novartis Investigative Site	Yvoir		Belgium	5530
15	Novartis Investigative Site	Amiens cedex 1		France	80054
16	Novartis Investigative Site	Caen Cedex		France	14033
17	Novartis Investigative Site	Grenoble		France	38043
18	Novartis Investigative Site	Lens Cedex		France	62307
19	Novartis Investigative Site	Lille		France	59037
20	Novartis Investigative Site	Lyon		France	69437
21	Novartis Investigative Site	Marseille		France	13273
22	Novartis Investigative Site	Nimes		France	30029
23	Novartis Investigative Site	Paris		France	75010
24	Novartis Investigative Site	Paris		France	75012
25	Novartis Investigative Site	Paris		France	75014
26	Novartis Investigative Site	Pessac		France	33600
27	Novartis Investigative Site	Poitiers Cedex		France	86021
28	Novartis Investigative Site	Rennes		France	F-35043
29	Novartis Investigative Site	Strasbourg		France	67091
30	Novartis Investigative Site	Toulouse Cedex		France	31059
31	Novartis Investigative Site	Villejuif Cedex		France	94805
32	Novartis Investigative Site	Berlin		Germany	13353
33	Novartis Investigative Site	Frankfurt/M		Germany	60590
34	Novartis Investigative Site	Köln		Germany	50937
35	Novartis Investigative Site	Magdeburg		Germany	39120
36	Novartis Investigative Site	Mainz		Germany	55131
37	Novartis Investigative Site	Muenster		Germany	48149
38	Novartis Investigative Site	Stuttgart		Germany	70376
39	Novartis Investigative Site	Tuebingen		Germany	72076
40	Novartis Investigative Site	Ulm		Germany	89081
41	Novartis Investigative Site	Pavia	(pv)	Italy	27100
42	Novartis Investigative Site	Monza	MB	Italy	20900
43	Novartis Investigative Site	Milano	MI	Italy	20162
44	Novartis Investigative Site	Florence		Italy	50134
45	Novartis Investigative Site	Orbassano		Italy	10043
46	Novartis Investigative Site	Pavia		Italy	27100
47	Novartis Investigative Site	Amsterdam		Netherlands	1081
48	Novartis Investigative Site	Den Haag		Netherlands	2545 CH
49	Novartis Investigative Site	Groningen		Netherlands	9713 GZ
50	Novartis Investigative Site	Maastricht		Netherlands	5800
51	Novartis Investigative Site	Nijmegen		Netherlands	6500 MB
52	Novartis Investigative Site	Rotterdam		Netherlands	3015 CE
53	Novartis Investigative Site	Barcelona	Catalunya	Spain	08036
54	Novartis Investigative Site	Valencia	Comunidad Valenciana	Spain	46010
55	Novartis Investigative Site	Majadahonda	Madrid	Spain	28222
56	Novartis Investigative Site	Göteborg		Sweden	SE-413 45
57	Novartis Investigative Site	Stockholm		Sweden	SE-118 83
58	Novartis Investigative Site	Belfast		United Kingdom	BT9 7AB
59	Novartis Investigative Site	Cambridge		United Kingdom	CB2 2QQ
60	Novartis Investigative Site	London		United Kingdom	SE1 9RT
61	Novartis Investigative Site	Oxford		United Kingdom	OX37LJ

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT00934544
• Other Study ID Numbers: CINC424A2352; CINCB 18424-352; 2009-009858-24
• First Posted: Jul 8, 2009
• Last Update Posted: Aug 19, 2019
• Last Verified: Jul 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Keywords provided by Novartis Pharmaceuticals: Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis
• Additional relevant MeSH terms: Polycythemia Vera; Primary Myelofibrosis

Study Results

Participant Flow

Recruitment Details	Subjects were recruited from 9 countries located in Europe: Austria, Belgium, France, Germany, Italy, Netherlands, Spain, Sweden, and United Kingdom.
Pre-assignment Detail	219 unique participants were randomized to either ruxolitinib or BAT. Of the 73 participants randomized to BAT, 45 were crossed over to ruxolitinib after a protocol-specified qualifying disease progression event.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)	Ruxolitinib After BAT (Cross-over)
Arm/Group Description	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule	Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
Period Title: Primary Endpoint Analysis (Interim)
STARTED	146	73	0
COMPLETED	91	31	0
NOT COMPLETED	55	42	0
Period Title: Primary Endpoint Analysis (Interim)
STARTED	146	28	45
Crossed Over After Qualifying Event	0	0	27
Crossed Over After AMEND 5	0	0	12
Crossed Over: Other	0	0	6
COMPLETED	39	0	11
NOT COMPLETED	107	28	34

Baseline Characteristics

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)	Total
Arm/Group Description	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule	Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.	Total of all reporting groups
Overall Participants	146	73	219
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.1 (9.74)	65.2 (10.27)	65.2 (9.89)
Sex: Female, Male (Count of Participants)
Female	63 43.2%	31 42.5%	94 42.9%
Male	83 56.8%	42 57.5%	125 57.1%
Disease Profile - Type of Myelofibrosis (MF) (Count of Participants)
Primary Myelofibrosis	77 52.7%	39 53.4%	116 53%
Post-polycythemia vera-myelofibrosis	48 32.9%	20 27.4%	68 31.1%
Post-essential thrombocythemia-myelofibrosis	21 14.4%	14 19.2%	35 16%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 48
Description	The change in spleen volume from baseline to week 48 was measured by magnetic resonance imaging (MRI) (or by computer tomography (CT) for participants unable to undergo MRI) and was calculated only for participants who had an evaluable spleen volume at baseline. The percentage of participants achieving a greater than or equal to 35% reduction in spleen volume from baseline to week 48 was then calculated by treatment group.
Time Frame	Baseline, Week 48

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. The table included participants with non-missing baseline MRI measurement of spleen volume only.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule	Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
Measure Participants	144	72
Number [Percentage of Participants]	28.5 19.5%	0 0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib, Best Available Therapy (BAT)
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Kaplan-Meir estimate
	Estimated Value	28.1
	Confidence Interval	(2-Sided) 95%; 21.3 to 36.6
	Parameter Dispersion	Type: Standard Deviation; Value: 22.123
	Estimation Comments

2. Secondary Outcome

Title	Duration of Maintenance of Spleen Volume Reduction (Median)
Description	DoMSR is defined as the interval between the first spleen volume measurement that is >=35% reduction from baseline and the first scan that is no longer = 35% reduction AND that is a >25% increase over nadir. It was evaluated using the Kaplan-Meier estimate for each treatment arm. The analysis was performed only for subjects who achieved greater than 35% reduction in spleen volume.
Time Frame	Baseline, up to Year 5

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule	Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
Measure Participants	78	1
Median (95% Confidence Interval) [years]	3.22	NA

3. Secondary Outcome

Title	Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)
Description	This is defined as the interval between randomization and date of the first MRI showing a 35% reduction from baseline in spleen volume. The analysis was performed for participants who achieved a 35% reduction in spleen volume.
Time Frame	Baseline, up to Year 5

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule	Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
Measure Participants	78	1
1.0 year	0.72	NA
1.5 years	0.67	NA
2.0 years	0.63	NA
2.5 years	0.54	NA
3.0 years	0.51	NA
3.5 years	0.48	NA
4.0 years	0.48	NA
4.5 years	0.48	NA
5.0 years	0.48	NA

4. Secondary Outcome

Title	Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24
Description	The change in spleen volume from baseline to week 24 was measured by magnetic resonance imaging (MRI) (or by computer tomography (CT) for participants unable to undergo MRI) and was calculated only for participants who had an evaluable spleen volume at baseline. The percentage of participants achieving a greater than or equal to 35% reduction in spleen volume from baseline to week 24 was then calculated by treatment group.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. The table included participants with non-missing baseline MRI measurement of spleen volume only.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule	Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
Measure Participants	144	72
Number [Percentage of Participants]	31.9 21.8%	0 0%

5. Secondary Outcome

Title	Time to First at Least 35% Reduction in Spleen Volume From Baseline by Treatment (Primary Analysis)
Description	This is defined as the interval between randomization and date of the first MRI showing at least 35% reduction from baseline in spleen volume. The analysis was performed for participants who achieved a 35% reduction in spleen volume
Time Frame	Time from randomization and date of the first MRI showing at least 35% reduction from baseline in spleen volume

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS)

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule	Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
Measure Participants	69	1
12 weeks	0.23	0
24 weeks	0.67	1
36 weeks	0.87	1
48 weeks	0.97	1

6. Secondary Outcome

Title	Progression-free Survival (PFS)
Description	Median of time progression free survival (95% CI), years
Time Frame	Time from randomization and the earliest of either increase in spleen volume >=25% from on-study nadir, splenic irradiation, splenectomy, leukemic transformation or death

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule	Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
Measure Participants	146	73
Median (95% Confidence Interval) [years]	1.6	1.4

7. Secondary Outcome

Title	Leukemia-free Survival (LFS)
Description	Time from randomization and earliest of either (1) date of bone marrow blast count of 20% or greater; (2) date of first peripheral blast count of 20% or greater that was subsequently confirmed to sustain for at least 8 weeks; (3) date of death from any cause
Time Frame	Time from randomization and earliest of either leukemia or death

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule	Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
Measure Participants	146	73
Median (95% Confidence Interval) [Years]	NA	4.1

8. Secondary Outcome

Title	Overall Survival (OS)
Description	Defined as the interval between randomization and the date of the bone marrow blast count of 20% or greater OR the date of the first peripheral blast count of 20% or greater that was subsequently confirmed to have been sustained for at least 8 weeks OR the date of death from any cause, whichever occurs first. OS was summarized using Kaplan-Meier estimates for each treatment arm. The estimates were supplemented by tables of number of events and probability estimates at several timepoints
Time Frame	From randomization until death from any cause

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria. Treatment groups were defined according to the treatment assignment at the time of randomization.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule	Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
Measure Participants	146	73
Median (95% Confidence Interval) [Years]	NA	4.1

9. Secondary Outcome

Title	Percentage of Participants With Bone Marrow Histomorphology at Week 48 (Primary Analysis)
Description	This was noted as fibrosis density and was tabulated by fibrosis grade at baseline and at week 48 (post-baseline). Descriptive statistics (participant percentages) were used. Fibrosis grades: 0 Scattered linear reticulin with no intersections corresponding to normal bone marrow ; 1 Loose network of reticulin with many intersections, especially in perivascular areas; 2 Diffuse and dense increase in reticulin with extensive intersections, occasionally with only focal bundles of collagen and/or focal osteosclerosis; 3 Diffuse and dense increase in reticulin with extensive intersections with coarse bundles of collagen, often associated with significant osteosclerosis
Time Frame	48 weeks

Outcome Measure Data

Analysis Population Description

Full analysis set (FAS) consisted of all subjects who were randomized and put in strata according to International Working Group for Myelofibrosis Research and Treatment(IWG MRT) prognostic criteria.

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule	Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
Measure Participants	146	73
Grade 0	2.7 1.8%	0.0 0%
Grade 1	7.5 5.1%	2.7 3.7%
Grade 2	8.9 6.1%	6.8 9.3%
Grade 3	24.0 16.4%	15.1 20.7%
Missing Grade	56.8 38.9%	75.3 103.2%

10. Secondary Outcome

Title	Bone Marrow Histomorphology
Description	Shift table from baseline to last available postbaseline fibrosis grade by treatment The grade gives an indication of the activity or amount of inflammation and the stage represents the amount of fibrosis or scarring. The grade is assigned a number based on the degree of inflammation, which is usually scored from 0-4 with 0 being no activity and 3 or 4 considered severe activity
Time Frame	Baseline, once a year

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS) Numbers of Participants Analyzed reflect only those participants who were randomized to either Ruxolitinib or Best Available Therapy and do not count those participants who could have crossed over to Ruxolitinib

Arm/Group Title	Ruxolitinib	Ruxolitinib - Grade 1	Ruxolitinib - Grade 2	Ruxolitinib - Grade 3	Ruxolitinib - Missing	Best Available Therapy (BAT) - Grade 0	Best Available Therapy (BAT) - Grade 1	Best Available Therapy (BAT) - Grade 2	Best Available Therapy (BAT) - Grade 3	Best Available Therapy - Missing
Arm/Group Description	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule
Measure Participants	146	146	146	146	146	73	73	73	73	73
Postbaseline Grade 0	1 0.7%	1 1.4%	2 0.9%	1 NaN	2 NaN	0 NaN	0 NaN	0 NaN	0 NaN	0 NaN
Postbaseline Grade 1	0 0%	10 13.7%	9 4.1%	2 NaN	0 NaN	0 NaN	1 NaN	0 NaN	1 NaN	0 NaN
Postbaseline Grade 2	0 0%	2 2.7%	8 3.7%	8 NaN	1 NaN	0 NaN	0 NaN	4 NaN	1 NaN	0 NaN
Postbaseline Grade 3	0 0%	6 8.2%	19 8.7%	28 NaN	2 NaN	0 NaN	0 NaN	4 NaN	8 NaN	3 NaN
Postbaseline Missing	2 1.4%	2 2.7%	17 7.8%	20 NaN	3 NaN	2 NaN	2 NaN	19 NaN	24 NaN	4 NaN

11. Secondary Outcome

Title	Duration of Follow-up by Treatment
Description	Number of Participants with duration of Follow up
Time Frame	baseline, 260 weeks (end of study)

Outcome Measure Data

Analysis Population Description

Safety Set Numbers of Participants Analyzed reflect only those participants who were randomized to either Ruxolitinib or Best Available Therapy and do not count those participants who could have crossed over to Ruxolitinib

Arm/Group Title	Ruxolitinib	Best Available Therapy (BAT)
Arm/Group Description	5 milligram tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule	Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment.
Measure Participants	146	73
<=1 year	16 11%	15 20.5%
>1 year - <=2 years	21 14.4%	10 13.7%
>2 years - <=3 years	9 6.2%	13 17.8%
>3 years - <=4 years	12 8.2%	5 6.8%
>4 years - <=5 years	27 18.5%	8 11%
5 years	61 41.8%	22 30.1%

Adverse Events

Arm/Group Title	Ruxolitinib Randomized		Ruxolitinib Randomized + Extension Phase		BAT Randomized		Ruxolitinib Cross-over
Arm/Group Description	Ruxolitinib Randomized		Ruxolitinib Randomized + Extension Phase		BAT Randomized		Ruxolitinib cross-over
All Cause Mortality
	Ruxolitinib Randomized		Ruxolitinib Randomized + Extension Phase		BAT Randomized		Ruxolitinib Cross-over
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Ruxolitinib Randomized		Ruxolitinib Randomized + Extension Phase		BAT Randomized		Ruxolitinib Cross-over
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/146 (34.9%)		85/146 (58.2%)		22/73 (30.1%)		20/45 (44.4%)
Blood and lymphatic system disorders
Anaemia	8/146 (5.5%)		10/146 (6.8%)		4/73 (5.5%)		2/45 (4.4%)
Anaemia of chronic disease	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Coagulopathy	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Febrile neutropenia	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Leukocytosis	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Lymphadenopathy	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Neutropenia	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Pancytopenia	2/146 (1.4%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Paratracheal lymphadenopathy	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Splenic infarction	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Splenomegaly	0/146 (0%)		2/146 (1.4%)		1/73 (1.4%)		1/45 (2.2%)
Thrombocytopenia	1/146 (0.7%)		2/146 (1.4%)		1/73 (1.4%)		4/45 (8.9%)
Thrombotic microangiopathy	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Cardiac disorders
Acute coronary syndrome	1/146 (0.7%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Aortic valve stenosis	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Arteriosclerosis coronary artery	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Atrial fibrillation	1/146 (0.7%)		4/146 (2.7%)		1/73 (1.4%)		0/45 (0%)
Atrial flutter	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Atrioventricular block	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Bradycardia	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Cardiac arrest	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Cardiac failure	3/146 (2.1%)		5/146 (3.4%)		1/73 (1.4%)		1/45 (2.2%)
Cardiopulmonary failure	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Congestive cardiomyopathy	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Coronary artery stenosis	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Hypertensive heart disease	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Ischaemic cardiomyopathy	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Myocardial infarction	0/146 (0%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Right ventricular failure	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Sick sinus syndrome	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Stress cardiomyopathy	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Supraventricular tachycardia	0/146 (0%)		3/146 (2.1%)		1/73 (1.4%)		0/45 (0%)
Ear and labyrinth disorders
Vertigo	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Eye disorders
Keratitis	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Ocular vascular disorder	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Visual impairment	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Gastrointestinal disorders
Abdominal pain	3/146 (2.1%)		6/146 (4.1%)		2/73 (2.7%)		1/45 (2.2%)
Abdominal pain upper	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		1/45 (2.2%)
Abdominal wall haematoma	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Anal fistula	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Ascites	0/146 (0%)		1/146 (0.7%)		2/73 (2.7%)		0/45 (0%)
Colitis ischaemic	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Constipation	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Diarrhoea	2/146 (1.4%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Enteritis	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Enterocolitis	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Faeces discoloured	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Gastric varices	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Gastritis haemorrhagic	1/146 (0.7%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Gastrointestinal haemorrhage	1/146 (0.7%)		1/146 (0.7%)		1/73 (1.4%)		1/45 (2.2%)
Gastrointestinal ulcer	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Haematemesis	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		1/45 (2.2%)
Haematochezia	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Haemorrhoids	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Ileus paralytic	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Incarcerated umbilical hernia	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Inguinal hernia	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Intestinal perforation	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Oesophageal haemorrhage	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Oesophageal varices haemorrhage	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Pancreatitis	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Peritoneal haemorrhage	0/146 (0%)		0/146 (0%)		2/73 (2.7%)		0/45 (0%)
Rectal haemorrhage	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Retroperitoneal haemorrhage	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Small intestinal perforation	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Subileus	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Umbilical hernia	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Upper gastrointestinal haemorrhage	2/146 (1.4%)		2/146 (1.4%)		0/73 (0%)		1/45 (2.2%)
Varices oesophageal	3/146 (2.1%)		4/146 (2.7%)		0/73 (0%)		1/45 (2.2%)
General disorders
Asthenia	1/146 (0.7%)		1/146 (0.7%)		1/73 (1.4%)		0/45 (0%)
Chest pain	1/146 (0.7%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Disease progression	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
General physical health deterioration	2/146 (1.4%)		4/146 (2.7%)		1/73 (1.4%)		0/45 (0%)
Generalised oedema	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Inflammation	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Multi-organ failure	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		1/45 (2.2%)
Oedema peripheral	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		1/45 (2.2%)
Performance status decreased	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Pyrexia	4/146 (2.7%)		5/146 (3.4%)		1/73 (1.4%)		1/45 (2.2%)
Hepatobiliary disorders
Cholecystitis	2/146 (1.4%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Cholelithiasis	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Hepatic failure	1/146 (0.7%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Hepatomegaly	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Portal hypertension	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Portal vein thrombosis	1/146 (0.7%)		2/146 (1.4%)		1/73 (1.4%)		0/45 (0%)
Infections and infestations
Bronchitis	3/146 (2.1%)		4/146 (2.7%)		1/73 (1.4%)		0/45 (0%)
Bronchopneumonia	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Campylobacter infection	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Cellulitis	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		1/45 (2.2%)
Clostridium difficile colitis	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Clostridium difficile infection	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Cystitis	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Endocarditis	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Enterococcal sepsis	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Escherichia infection	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Escherichia urinary tract infection	0/146 (0%)		0/146 (0%)		0/73 (0%)		2/45 (4.4%)
Febrile infection	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Gastroenteritis	2/146 (1.4%)		3/146 (2.1%)		0/73 (0%)		0/45 (0%)
Gastroenteritis clostridial	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Gastroenteritis norovirus	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Gastrointestinal infection	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Genital infection female	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Herpes zoster	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Infection	0/146 (0%)		3/146 (2.1%)		0/73 (0%)		1/45 (2.2%)
Influenza	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Klebsiella sepsis	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Lung infection	2/146 (1.4%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Meningitis	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Meningoencephalitis herpetic	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Neutropenic sepsis	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Oesophageal infection	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Peritonitis	0/146 (0%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Pneumocystis jirovecii pneumonia	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Pneumonia	2/146 (1.4%)		11/146 (7.5%)		4/73 (5.5%)		1/45 (2.2%)
Pneumonia mycoplasmal	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Postoperative abscess	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Pseudomonal sepsis	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Pyelonephritis	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Respiratory tract infection	2/146 (1.4%)		3/146 (2.1%)		0/73 (0%)		0/45 (0%)
Sepsis	0/146 (0%)		2/146 (1.4%)		0/73 (0%)		1/45 (2.2%)
Sepsis syndrome	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Septic shock	1/146 (0.7%)		2/146 (1.4%)		0/73 (0%)		1/45 (2.2%)
Skin infection	1/146 (0.7%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Soft tissue infection	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Staphylococcal infection	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Staphylococcal sepsis	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Testicular abscess	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Tuberculosis	1/146 (0.7%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Urinary tract infection	1/146 (0.7%)		2/146 (1.4%)		0/73 (0%)		1/45 (2.2%)
Urinary tract infection bacterial	2/146 (1.4%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Urosepsis	1/146 (0.7%)		3/146 (2.1%)		0/73 (0%)		0/45 (0%)
Viral infection	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Injury, poisoning and procedural complications
Concussion	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Ear injury	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Femoral neck fracture	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Femur fracture	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Head injury	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Hip fracture	1/146 (0.7%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Injury	1/146 (0.7%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Lumbar vertebral fracture	0/146 (0%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Post procedural haemorrhage	1/146 (0.7%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Post-traumatic pain	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Postoperative fever	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Postoperative respiratory distress	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Procedural pain	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Radius fracture	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Seroma	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Thoracic vertebral fracture	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Traumatic fracture	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Traumatic haematoma	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Traumatic intracranial haemorrhage	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Investigations
Alanine aminotransferase increased	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Blood creatinine increased	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
C-reactive protein increased	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Gamma-glutamyltransferase increased	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Haemoglobin decreased	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Weight increased	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Metabolism and nutrition disorders
Fluid retention	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Hyperkalaemia	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Hyperuricaemia	0/146 (0%)		3/146 (2.1%)		0/73 (0%)		0/45 (0%)
Hyponatraemia	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Back pain	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		1/45 (2.2%)
Bone pain	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Groin pain	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Intervertebral disc protrusion	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Osteitis	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Osteolysis	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Osteonecrosis	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute myeloid leukaemia	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Basal cell carcinoma	1/146 (0.7%)		4/146 (2.7%)		0/73 (0%)		0/45 (0%)
Bowen's disease	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Bronchial carcinoma	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Carcinoma in situ	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Cholesteatoma	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Gastric cancer	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Glioblastoma multiforme	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Lung adenocarcinoma recurrent	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Lung neoplasm malignant	0/146 (0%)		1/146 (0.7%)		1/73 (1.4%)		0/45 (0%)
Malignant melanoma	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Metastases to lymph nodes	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Metastases to peritoneum	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Metastases to spine	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Metastatic squamous cell carcinoma	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Myelofibrosis	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Neuroendocrine carcinoma metastatic	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Prostate cancer	1/146 (0.7%)		4/146 (2.7%)		0/73 (0%)		0/45 (0%)
Squamous cell carcinoma of skin	3/146 (2.1%)		5/146 (3.4%)		1/73 (1.4%)		0/45 (0%)
Nervous system disorders
Aphasia	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Cerebral haemorrhage	2/146 (1.4%)		2/146 (1.4%)		0/73 (0%)		1/45 (2.2%)
Cerebrovascular accident	1/146 (0.7%)		4/146 (2.7%)		0/73 (0%)		0/45 (0%)
Coma	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Convulsion	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Depressed level of consciousness	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Encephalopathy	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Epilepsy	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Hepatic encephalopathy	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Paraesthesia	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Pseudoradicular syndrome	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Somnolence	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Syncope	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Psychiatric disorders
Abnormal behaviour	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Confusional state	1/146 (0.7%)		3/146 (2.1%)		0/73 (0%)		0/45 (0%)
Delusion	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Depression	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Renal and urinary disorders
Hydronephrosis	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Nephrolithiasis	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Prerenal failure	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Renal failure	1/146 (0.7%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Renal failure acute	3/146 (2.1%)		4/146 (2.7%)		1/73 (1.4%)		3/45 (6.7%)
Renal failure chronic	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Renal impairment	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Renal infarct	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Urinary retention	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Reproductive system and breast disorders
Benign prostatic hyperplasia	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Uterine prolapse	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Cough	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Dyspnoea	2/146 (1.4%)		4/146 (2.7%)		3/73 (4.1%)		0/45 (0%)
Interstitial lung disease	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Lung disorder	0/146 (0%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Lung infiltration	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Pleural effusion	1/146 (0.7%)		1/146 (0.7%)		1/73 (1.4%)		1/45 (2.2%)
Pleurisy	0/146 (0%)		2/146 (1.4%)		0/73 (0%)		0/45 (0%)
Pneumonitis	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Productive cough	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Pulmonary embolism	1/146 (0.7%)		4/146 (2.7%)		0/73 (0%)		0/45 (0%)
Pulmonary hypertension	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Pulmonary oedema	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		1/45 (2.2%)
Respiratory distress	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Respiratory failure	0/146 (0%)		1/146 (0.7%)		2/73 (2.7%)		0/45 (0%)
Tachypnoea	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Skin and subcutaneous tissue disorders
Actinic keratosis	0/146 (0%)		0/146 (0%)		2/73 (2.7%)		0/45 (0%)
Vascular disorders
Aortic aneurysm	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Aortic thrombosis	0/146 (0%)		0/146 (0%)		1/73 (1.4%)		0/45 (0%)
Arterial stenosis	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Circulatory collapse	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Hypertension	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Hypertensive crisis	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Intra-abdominal haematoma	0/146 (0%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Thrombosis	0/146 (0%)		0/146 (0%)		0/73 (0%)		1/45 (2.2%)
Venous thrombosis	1/146 (0.7%)		1/146 (0.7%)		0/73 (0%)		0/45 (0%)
Other (Not Including Serious) Adverse Events
	Ruxolitinib Randomized		Ruxolitinib Randomized + Extension Phase		BAT Randomized		Ruxolitinib Cross-over
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	145/146 (99.3%)		145/146 (99.3%)		64/73 (87.7%)		42/45 (93.3%)
Blood and lymphatic system disorders
Anaemia	61/146 (41.8%)		71/146 (48.6%)		8/73 (11%)		19/45 (42.2%)
Leukocytosis	7/146 (4.8%)		8/146 (5.5%)		0/73 (0%)		2/45 (4.4%)
Thrombocytopenia	67/146 (45.9%)		77/146 (52.7%)		10/73 (13.7%)		21/45 (46.7%)
Cardiac disorders
Angina pectoris	5/146 (3.4%)		8/146 (5.5%)		1/73 (1.4%)		2/45 (4.4%)
Atrial fibrillation	2/146 (1.4%)		11/146 (7.5%)		1/73 (1.4%)		1/45 (2.2%)
Palpitations	8/146 (5.5%)		12/146 (8.2%)		0/73 (0%)		2/45 (4.4%)
Tachycardia	4/146 (2.7%)		8/146 (5.5%)		4/73 (5.5%)		1/45 (2.2%)
Ear and labyrinth disorders
Vertigo	5/146 (3.4%)		9/146 (6.2%)		1/73 (1.4%)		1/45 (2.2%)
Gastrointestinal disorders
Abdominal distension	7/146 (4.8%)		11/146 (7.5%)		3/73 (4.1%)		3/45 (6.7%)
Abdominal pain	14/146 (9.6%)		21/146 (14.4%)		12/73 (16.4%)		3/45 (6.7%)
Abdominal pain upper	12/146 (8.2%)		16/146 (11%)		4/73 (5.5%)		5/45 (11.1%)
Ascites	4/146 (2.7%)		6/146 (4.1%)		3/73 (4.1%)		3/45 (6.7%)
Constipation	12/146 (8.2%)		19/146 (13%)		3/73 (4.1%)		2/45 (4.4%)
Diarrhoea	36/146 (24.7%)		55/146 (37.7%)		13/73 (17.8%)		12/45 (26.7%)
Dyspepsia	7/146 (4.8%)		10/146 (6.8%)		4/73 (5.5%)		3/45 (6.7%)
Gastrooesophageal reflux disease	4/146 (2.7%)		10/146 (6.8%)		0/73 (0%)		2/45 (4.4%)
Nausea	21/146 (14.4%)		30/146 (20.5%)		7/73 (9.6%)		5/45 (11.1%)
Vomiting	16/146 (11%)		27/146 (18.5%)		1/73 (1.4%)		4/45 (8.9%)
General disorders
Asthenia	28/146 (19.2%)		38/146 (26%)		9/73 (12.3%)		10/45 (22.2%)
Chest pain	0/146 (0%)		0/146 (0%)		4/73 (5.5%)		4/45 (8.9%)
Chills	4/146 (2.7%)		8/146 (5.5%)		0/73 (0%)		0/45 (0%)
Fatigue	23/146 (15.8%)		36/146 (24.7%)		8/73 (11%)		8/45 (17.8%)
General physical health deterioration	3/146 (2.1%)		7/146 (4.8%)		4/73 (5.5%)		3/45 (6.7%)
Oedema peripheral	33/146 (22.6%)		55/146 (37.7%)		21/73 (28.8%)		8/45 (17.8%)
Peripheral swelling	3/146 (2.1%)		7/146 (4.8%)		0/73 (0%)		3/45 (6.7%)
Pyrexia	20/146 (13.7%)		36/146 (24.7%)		6/73 (8.2%)		7/45 (15.6%)
Infections and infestations
Bronchitis	15/146 (10.3%)		37/146 (25.3%)		5/73 (6.8%)		3/45 (6.7%)
Cystitis	9/146 (6.2%)		15/146 (10.3%)		3/73 (4.1%)		1/45 (2.2%)
Gastroenteritis	9/146 (6.2%)		14/146 (9.6%)		1/73 (1.4%)		1/45 (2.2%)
Herpes zoster	9/146 (6.2%)		16/146 (11%)		0/73 (0%)		5/45 (11.1%)
Lower respiratory tract infection	2/146 (1.4%)		2/146 (1.4%)		0/73 (0%)		3/45 (6.7%)
Nasopharyngitis	27/146 (18.5%)		40/146 (27.4%)		9/73 (12.3%)		4/45 (8.9%)
Respiratory tract infection	6/146 (4.1%)		9/146 (6.2%)		3/73 (4.1%)		2/45 (4.4%)
Rhinitis	7/146 (4.8%)		9/146 (6.2%)		0/73 (0%)		1/45 (2.2%)
Upper respiratory tract infection	6/146 (4.1%)		9/146 (6.2%)		1/73 (1.4%)		2/45 (4.4%)
Urinary tract infection	11/146 (7.5%)		19/146 (13%)		2/73 (2.7%)		6/45 (13.3%)
Injury, poisoning and procedural complications
Fall	4/146 (2.7%)		8/146 (5.5%)		1/73 (1.4%)		1/45 (2.2%)
Investigations
Alanine aminotransferase increased	2/146 (1.4%)		3/146 (2.1%)		0/73 (0%)		3/45 (6.7%)
Aspartate aminotransferase increased	1/146 (0.7%)		3/146 (2.1%)		0/73 (0%)		3/45 (6.7%)
Blood alkaline phosphatase increased	3/146 (2.1%)		3/146 (2.1%)		0/73 (0%)		3/45 (6.7%)
Cardiac murmur	6/146 (4.1%)		8/146 (5.5%)		3/73 (4.1%)		3/45 (6.7%)
Gamma-glutamyltransferase increased	7/146 (4.8%)		11/146 (7.5%)		1/73 (1.4%)		1/45 (2.2%)
Haemoglobin decreased	4/146 (2.7%)		6/146 (4.1%)		3/73 (4.1%)		4/45 (8.9%)
Platelet count decreased	11/146 (7.5%)		12/146 (8.2%)		2/73 (2.7%)		9/45 (20%)
Weight decreased	3/146 (2.1%)		8/146 (5.5%)		6/73 (8.2%)		2/45 (4.4%)
Weight increased	23/146 (15.8%)		29/146 (19.9%)		1/73 (1.4%)		5/45 (11.1%)
White blood cell count increased	3/146 (2.1%)		4/146 (2.7%)		0/73 (0%)		4/45 (8.9%)
Metabolism and nutrition disorders
Decreased appetite	6/146 (4.1%)		20/146 (13.7%)		4/73 (5.5%)		4/45 (8.9%)
Gout	1/146 (0.7%)		6/146 (4.1%)		1/73 (1.4%)		3/45 (6.7%)
Hyperuricaemia	1/146 (0.7%)		8/146 (5.5%)		1/73 (1.4%)		0/45 (0%)
Iron overload	2/146 (1.4%)		5/146 (3.4%)		0/73 (0%)		3/45 (6.7%)
Musculoskeletal and connective tissue disorders
Arthralgia	19/146 (13%)		30/146 (20.5%)		8/73 (11%)		7/45 (15.6%)
Back pain	18/146 (12.3%)		24/146 (16.4%)		10/73 (13.7%)		3/45 (6.7%)
Bone pain	9/146 (6.2%)		9/146 (6.2%)		4/73 (5.5%)		2/45 (4.4%)
Muscle spasms	15/146 (10.3%)		28/146 (19.2%)		5/73 (6.8%)		4/45 (8.9%)
Musculoskeletal chest pain	4/146 (2.7%)		8/146 (5.5%)		1/73 (1.4%)		3/45 (6.7%)
Musculoskeletal pain	7/146 (4.8%)		11/146 (7.5%)		1/73 (1.4%)		1/45 (2.2%)
Osteoarthritis	3/146 (2.1%)		9/146 (6.2%)		1/73 (1.4%)		1/45 (2.2%)
Pain in extremity	18/146 (12.3%)		24/146 (16.4%)		4/73 (5.5%)		11/45 (24.4%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	5/146 (3.4%)		11/146 (7.5%)		1/73 (1.4%)		1/45 (2.2%)
Squamous cell carcinoma of skin	3/146 (2.1%)		10/146 (6.8%)		1/73 (1.4%)		0/45 (0%)
Nervous system disorders
Dizziness	12/146 (8.2%)		20/146 (13.7%)		5/73 (6.8%)		6/45 (13.3%)
Headache	18/146 (12.3%)		23/146 (15.8%)		4/73 (5.5%)		8/45 (17.8%)
Paraesthesia	10/146 (6.8%)		16/146 (11%)		4/73 (5.5%)		4/45 (8.9%)
Sciatica	5/146 (3.4%)		9/146 (6.2%)		1/73 (1.4%)		0/45 (0%)
Psychiatric disorders
Anxiety	5/146 (3.4%)		9/146 (6.2%)		0/73 (0%)		1/45 (2.2%)
Insomnia	9/146 (6.2%)		13/146 (8.9%)		7/73 (9.6%)		5/45 (11.1%)
Respiratory, thoracic and mediastinal disorders
Cough	22/146 (15.1%)		38/146 (26%)		12/73 (16.4%)		9/45 (20%)
Dyspnoea	22/146 (15.1%)		35/146 (24%)		13/73 (17.8%)		12/45 (26.7%)
Dyspnoea exertional	11/146 (7.5%)		13/146 (8.9%)		2/73 (2.7%)		1/45 (2.2%)
Epistaxis	13/146 (8.9%)		18/146 (12.3%)		5/73 (6.8%)		6/45 (13.3%)
Oropharyngeal pain	4/146 (2.7%)		8/146 (5.5%)		3/73 (4.1%)		2/45 (4.4%)
Rales	6/146 (4.1%)		8/146 (5.5%)		1/73 (1.4%)		2/45 (4.4%)
Skin and subcutaneous tissue disorders
Ecchymosis	3/146 (2.1%)		8/146 (5.5%)		0/73 (0%)		4/45 (8.9%)
Eczema	1/146 (0.7%)		3/146 (2.1%)		4/73 (5.5%)		4/45 (8.9%)
Hyperhidrosis	3/146 (2.1%)		11/146 (7.5%)		0/73 (0%)		1/45 (2.2%)
Night sweats	14/146 (9.6%)		27/146 (18.5%)		6/73 (8.2%)		4/45 (8.9%)
Pruritus	9/146 (6.2%)		17/146 (11.6%)		13/73 (17.8%)		4/45 (8.9%)
Rash	8/146 (5.5%)		12/146 (8.2%)		1/73 (1.4%)		2/45 (4.4%)
Rosacea	2/146 (1.4%)		4/146 (2.7%)		1/73 (1.4%)		3/45 (6.7%)
Skin lesion	2/146 (1.4%)		12/146 (8.2%)		0/73 (0%)		2/45 (4.4%)
Vascular disorders
Haematoma	15/146 (10.3%)		22/146 (15.1%)		3/73 (4.1%)		4/45 (8.9%)
Hypertension	8/146 (5.5%)		19/146 (13%)		3/73 (4.1%)		2/45 (4.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.