Asian Phase II Study of INC424 in Patients With Primary Myelofibrosis (MF), Post-PV MF or Post-ET MF

• Sponsor: Novartis Pharmaceuticals (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01392443
• Collaborator: (none)
• Enrollment: 120
• Locations: 26
• Arm: 1
• Actual Duration (Months): 84.6
• Patients Per Site: 4.6
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The objective of this study was to determine the efficacy of INC424 as assessed by reduction in spleen volume in patients with primary myelofibrosis (MF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF. The safety and tolerability of INC424 and the effects of INC424 on patient reported outcomes and the duration of response as assessed by reduction in spleen volume was also assessed.

Condition or Disease	Intervention/Treatment	Phase
Primary Myelofibrosis (MF); Post-Polycythemia Vera (PV) MF; Post-Essential Thrombocythemia (ET) MF	Drug: Ruxolitinib	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Multi-national Open-label Phase II Study of the JAK Inhibitor INC424 in Patients With Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis or Post-essential Thrombocythemia Myelofibrosis
• Actual Study Start Date: Oct 14, 2010
• Actual Primary Completion Date: Oct 31, 2017
• Actual Study Completion Date: Oct 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ruxolitinib Ruxolitinib was taken twice daily, unless instructed. Starting dose 15 mg BID for patients with baseline platelet count of 100,000/μL to 200,000/μL (inclusive) or 20 mg BID for those with baseline platelet count >200,000/μL (approximately 12 hours apart: morning and night), increased or decreased per standardized dosing paradigm.	Drug: Ruxolitinib; INC424 Tablet for oral use, provided in 5 mg bottles. The dosage strength was 5 mg/tablet INC424 phosphate (free base equivalent).; Other Names: INC424

Outcome Measures

Primary Outcome Measures

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

   The primary measure of spleen size was by MRI. MRIs were performed with a body coil because the objective was to measure organ volume only, not to assess for lesions. MRIs were performed by local radiologists who were instructed not to provide a quantitative measure of spleen volume, but could provide a qualitative assessment such as enlarged, smaller, larger, etc. The scans from an individual patient were to be read by a central reader upon transfer from the site radiologist.

Secondary Outcome Measures

1. Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Each Scheduled Time Point - Best Response [Weeks 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, at any time point]

   The best response rate was defined as the proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline at any post-baseline assessment. The best response rate was estimated with an associated 95% confidence interval.

2. Kaplan Meier Estimates of Duration of Response of at Least ≥ 35% Reduction From Baseline in Spleen Volume Per Kaplan Meier Estimates [Weeks 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240]

   For patients who had at least one ≥ 35% reduction in spleen volume from baseline at postbaseline, the duration of response was calculated. The start date of the duration was defined as the first spleen volume measurement that was ≥ 35% reduction from baseline, and the end date of the response duration was defined as the earliest of the following: death, A ≥ 25% increase in spleen volume by MRI (or CT in applicable patients) compared to baseline, Splenic irradiation, Leukemic transformation as defined by a bone marrow or a peripheral blood blast count of ≥ 20%, Splenectomy. Duration of response is calculated only for participants who achieved at least one measured >= 35% reduction in spleen volume at any time.

3. Change in EORTC QLQ-C30 Scores From Baseline in at Week 24 [Baseline, Week 24]

   Patient reported outcomes regarding the impact of MF on patients were assessed using the EORTC QLQ-C30. Data from the EORTC QLQ-C30 questionnaire was analyzed using the standardized scores. There were 2 categories to this scale: Functional/QOL scale and Symptom and Other items scale. For each sub-scale, the raw scores were standardized in order to obtain scores ranging from 0 to 100. For Functional/QOL subscales: a higher score represents a higher/better level of functioning. For Symptoms and Other items subscales: a higher score represents worse level of symptoms. The absolute change from baseline was calculated for each scale and summarized descriptively by scheduled visit.

4. Change in Total Symptom Score From Baseline at Week 24 as Measured by Seven-day Modified MFSAF v2.0 [Baseline, Week 24]

   The Seven-day modified MFSAF v2.0 is a 7-item PRO instrument based on the modified MFSAF v2.0 diary administered at specified visits. Symptoms of myelofibrosis (MF) were assessed using this instrument & included filling up quickly/early satiety, abdominal discomfort, pain under the ribs, night sweats, itching, bone/muscle pain & inactivity. The first 6 items assessed MF symptom severity at its worst as recalled & the seventh captured MF-related inactivity in the 7 days prior to the clinic visit assessment. All 7 items asked subjects to record their answers on an 11-point numeric rating scale (NRS) (0=Absent, 10=Worst Imaginable). The first 6 items of the instrument focus on MF symptoms & are summed to create a Total Symptom score, defined as the sum of the 6 individual symptom scores other than the inactivity score (each with 0-10 point scale) collected on the same week. The total symptom scale ranges from 0 -60 where higher score indicates a worse level of the condition.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. 18 years or older

2. Diagnosis of primary myelofibrosis (MF), post-polycythemia vera (PV) MF, or post-essential thrombocythemia (ET) MF

3. Enlarged spleen, measuring 5 cm or greater from the costal margin

4. Must have two or more of the following risk factors:

5. Over 65 years old

6. Have the following symptoms often associated with MF: loss of weight, fever, night sweats

7. Have a low red blood cell count (anemia - hemoglobin < 10 g/dL)

8. Have a high white blood cell count (history of white blood cell count > 25,000/uL)

9. Have high circulating blasts (> or = 1%) as measured by blood tests

10. Should have circulating blasts <10% (as measured by blood tests)

11. Should be capable of self-care

12. Should have adequate bone marrow reserve

13. Should not have the option of stem cell transplantation

14. Should discontinue any prior or ongoing treatment for myelofibrosis prior to entering the study

15. Had no prior treatment with another JAK inhibitor

Exclusion Criteria:

1. Does not have adequate liver or kidney function (as measured by blood tests)

2. Has an active infection (bacterial, viral, etc.)

3. Has active hepatitis A, B, or C or positive for HIV

4. Has another cancer that needs active intervention

5. Had a history of bleeding disorder

6. Had a history of very low platelet counts (as measured by blood tests) not related to treatment of MF

7. Had radiation of the spleen within 1 year of joining the study

8. Does not have adequate heart function

9. Sufficient time has elapsed between stopping previous treatment for MF and joining the study

10. Females who are pregnant or breast-feeding

11. Not able to sign informed consent

12. Has any other active medical conditions that the doctor deems may compromise your safety or ability to join in the study

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Beijing	Beijing	China	100730
2	Novartis Investigative Site	Guangzhou	Guangdong	China	51000
3	Novartis Investigative Site	Wuhan	Hubei	China	430030
4	Novartis Investigative Site	Nanjing	Jiangsu	China	210029
5	Novartis Investigative Site	Suzhou	Jiangsu	China	215006
6	Novartis Investigative Site	Chengdu	Sichuan	China	610041
7	Novartis Investigative Site	Tianjin	Tianjin	China	300020
8	Novartis Investigative Site	Hangzhou	Zhejiang	China	310003
9	Novartis Investigative Site	Jinan		China	250012
10	Novartis Investigative Site	Shanghai		China	200025
11	Novartis Investigative Site	Nagoya	Aichi	Japan	466 8560
12	Novartis Investigative Site	Fukuoka city	Fukuoka	Japan	812-8582
13	Novartis Investigative Site	Maebashi city	Gunma	Japan	371 8511
14	Novartis Investigative Site	Kanazawa-city	Ishikawa	Japan	920-8641
15	Novartis Investigative Site	Tsu-city	Mie	Japan	514-8507
16	Novartis Investigative Site	Suita city	Osaka	Japan	565 0871
17	Novartis Investigative Site	Bunkyo ku	Tokyo	Japan	113 8655
18	Novartis Investigative Site	Shinjuku-ku	Tokyo	Japan	160 8582
19	Novartis Investigative Site	Shinjuku-ku	Tokyo	Japan	160-0023
20	Novartis Investigative Site	Seoul	Korea	Korea, Republic of	06351
21	Novartis Investigative Site	Seoul	Seocho Gu	Korea, Republic of	06591
22	Novartis Investigative Site	Seoul		Korea, Republic of	03080
23	Novartis Investigative Site	Seoul		Korea, Republic of	03722
24	Novartis Investigative Site	Kaohsiung		Taiwan	833
25	Novartis Investigative Site	Taipei		Taiwan	10048
26	Novartis Investigative Site	Taoyuan		Taiwan	333

Sponsors and Collaborators

• Novartis Pharmaceuticals

Investigators

• Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Study Documents (Full-Text)

• Study Protocol - Apr 15, 2011
• Statistical Analysis Plan - Aug 4, 2017

More Information

Publications

None provided.

• Responsible Party: Novartis Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT01392443
• Other Study ID Numbers: CINC424A2202
• First Posted: Jul 12, 2011
• Last Update Posted: Sep 3, 2019
• Last Verified: Aug 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Undecided
• Plan to Share IPD: Undecided
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Novartis Pharmaceuticals: Primary Myelofibrosis (MF); Post-Polycythemia Vera (PV) MF; Post-Essential Thrombocythemia (ET) MF; post-PV MF; post-ET MF; INC424; Ruxolitinib; Myelofibrosis; MF
• Additional relevant MeSH terms: Polycythemia Vera; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential

Study Results

Participant Flow

Recruitment Details	A total of 110 patients were planned, 120 patients were enrolled and analyzed.

Arm/Group Title	Ruxolitinib
Arm/Group Description	Ruxolitinib was taken twice daily, unless instructed. Starting dose 15 mg BID for patients with baseline platelet count of 100,000/μL to 200,000/μL (inclusive) or 20 mg BID for those with baseline platelet count >200,000/μL (approximately 12 hours apart: morning and night), increased or decreased per standardized dosing paradigm.
Period Title: Overall Study
STARTED	120
COMPLETED	52
NOT COMPLETED	68

Baseline Characteristics

Arm/Group Title	Ruxolitinib
Arm/Group Description	Ruxolitinib was taken twice daily, unless instructed. Starting dose 15 mg BID for patients with baseline platelet count of 100,000/μL to 200,000/μL (inclusive) or 20 mg BID for those with baseline platelet count >200,000/μL (approximately 12 hours apart: morning and night), increased or decreased per standardized dosing paradigm.
Overall Participants	120
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	59.0 (12.25)
Sex: Female, Male (Count of Participants)
Female	62 51.7%
Male	58 48.3%
Race/Ethnicity, Customized (Number) [Number]
Japanese	30 25%
Korean	17 14.2%
Chinese	63 52.5%
Taiwanese	10 8.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24
Description	The primary measure of spleen size was by MRI. MRIs were performed with a body coil because the objective was to measure organ volume only, not to assess for lesions. MRIs were performed by local radiologists who were instructed not to provide a quantitative measure of spleen volume, but could provide a qualitative assessment such as enlarged, smaller, larger, etc. The scans from an individual patient were to be read by a central reader upon transfer from the site radiologist.
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): comprised of all patients who received at least one dose of ruxolitinib.

Arm/Group Title	Ruxolitinib
Arm/Group Description	Ruxolitinib was taken twice daily, unless instructed. Starting dose 15 mg BID for patients with baseline platelet count of 100,000/μL to 200,000/μL (inclusive) or 20 mg BID for those with baseline platelet count >200,000/μL (approximately 12 hours apart: morning and night), increased or decreased per standardized dosing paradigm.
Measure Participants	120
Count of Participants [Participants]	38 31.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Ruxolitinib
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0007
	Comments
	Method	single-sample biniminal test
	Comments

2. Secondary Outcome

Title	Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Each Scheduled Time Point - Best Response
Description	The best response rate was defined as the proportion of patients achieving a ≥ 35% reduction in spleen volume from baseline at any post-baseline assessment. The best response rate was estimated with an associated 95% confidence interval.
Time Frame	Weeks 24, 36, 48, 72, 96, 120, 144, 168, 192, 216, 240, at any time point

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): comprised of all patients who received at least one dose of ruxolitinib.

Arm/Group Title	Ruxolitinib
Arm/Group Description	Ruxolitinib was taken twice daily, unless instructed. Starting dose 15 mg BID for patients with baseline platelet count of 100,000/μL to 200,000/μL (inclusive) or 20 mg BID for those with baseline platelet count >200,000/μL (approximately 12 hours apart: morning and night), increased or decreased per standardized dosing paradigm.
Measure Participants	120
Week 24	35.8 29.8%
Week 36	40.0 33.3%
Week 48	44.2 36.8%
Week 72	44.2 36.8%
Week 96	45.8 38.2%
Week 120	45.8 38.2%
Week 144	46.7 38.9%
Week 168	47.5 39.6%
Week 192	47.5 39.6%
Week 216	47.5 39.6%
Week 240	47.5 39.6%
at any time point	47.5 39.6%

3. Secondary Outcome

Title	Kaplan Meier Estimates of Duration of Response of at Least ≥ 35% Reduction From Baseline in Spleen Volume Per Kaplan Meier Estimates
Description	For patients who had at least one ≥ 35% reduction in spleen volume from baseline at postbaseline, the duration of response was calculated. The start date of the duration was defined as the first spleen volume measurement that was ≥ 35% reduction from baseline, and the end date of the response duration was defined as the earliest of the following: death, A ≥ 25% increase in spleen volume by MRI (or CT in applicable patients) compared to baseline, Splenic irradiation, Leukemic transformation as defined by a bone marrow or a peripheral blood blast count of ≥ 20%, Splenectomy. Duration of response is calculated only for participants who achieved at least one measured >= 35% reduction in spleen volume at any time.
Time Frame	Weeks 12, 24, 36, 48, 60, 72, 84, 96, 120, 144, 168, 192, 216, 240

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): comprised of all patients who received at least one dose of ruxolitinib.

Arm/Group Title	Ruxolitinib
Arm/Group Description	Ruxolitinib was taken twice daily, unless instructed. Starting dose 15 mg BID for patients with baseline platelet count of 100,000/μL to 200,000/μL (inclusive) or 20 mg BID for those with baseline platelet count >200,000/μL (approximately 12 hours apart: morning and night), increased or decreased per standardized dosing paradigm.
Measure Participants	120
12 weeks	1.00
24 weeks	0.96
36 weeks	0.96
48 weeks	0.93
60 weeks	0.93
72 weeks	0.91
84 weeks	0.89
96 weeks	0.89
120 weeks	0.89
144 weeks	0.85
168 weeks	0.79
192 weeks	0.75
216 weeks	0.75
240 weeks	NA

4. Secondary Outcome

Title	Change in EORTC QLQ-C30 Scores From Baseline in at Week 24
Description	Patient reported outcomes regarding the impact of MF on patients were assessed using the EORTC QLQ-C30. Data from the EORTC QLQ-C30 questionnaire was analyzed using the standardized scores. There were 2 categories to this scale: Functional/QOL scale and Symptom and Other items scale. For each sub-scale, the raw scores were standardized in order to obtain scores ranging from 0 to 100. For Functional/QOL subscales: a higher score represents a higher/better level of functioning. For Symptoms and Other items subscales: a higher score represents worse level of symptoms. The absolute change from baseline was calculated for each scale and summarized descriptively by scheduled visit.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): comprised of all patients who received at least one dose of ruxolitinib.

Arm/Group Title	Ruxolitinib
Arm/Group Description	Ruxolitinib was taken twice daily, unless instructed. Starting dose 15 mg BID for patients with baseline platelet count of 100,000/μL to 200,000/μL (inclusive) or 20 mg BID for those with baseline platelet count >200,000/μL (approximately 12 hours apart: morning and night), increased or decreased per standardized dosing paradigm.
Measure Participants	120
Func./QOL scales: Global Health Status/QOL	5.2 (22.04)
Func./QOL scales: Physical Functioning	0.6 (14.70)
Func./QOL scales:Role Functioning	-0.2 (21.54)
Func./QOL scales: Emotional Functioning	1.9 (14.14)
Func./QOL scales: Cognitive Functioning	-4.0 (18.43)
Func./QOL scales: Social Functioning	0.2 (21.41)
Symptom and Other items: Fatigue	-1.3 (20.32)
Symptom & Other items: Nausea and Vomiting	0.0 (9.43)
Symptom and Other items: Pain	-1.8 (18.99)
Symptom and Other items: Dyspnea	2.3 (25.93)
Symptom and Other items: Insomnia	-2.0 (30.12)
Symptom and Other items: Appetite Loss	-6.3 (25.26)
Symptom and Other items: Constipation	4.6 (20.02)
Symptom and Other items: Diarrhea	1.7 (23.75)
Symptom & Other items: Fin. difficulties	-2.0 (23.49)

5. Secondary Outcome

Title	Change in Total Symptom Score From Baseline at Week 24 as Measured by Seven-day Modified MFSAF v2.0
Description	The Seven-day modified MFSAF v2.0 is a 7-item PRO instrument based on the modified MFSAF v2.0 diary administered at specified visits. Symptoms of myelofibrosis (MF) were assessed using this instrument & included filling up quickly/early satiety, abdominal discomfort, pain under the ribs, night sweats, itching, bone/muscle pain & inactivity. The first 6 items assessed MF symptom severity at its worst as recalled & the seventh captured MF-related inactivity in the 7 days prior to the clinic visit assessment. All 7 items asked subjects to record their answers on an 11-point numeric rating scale (NRS) (0=Absent, 10=Worst Imaginable). The first 6 items of the instrument focus on MF symptoms & are summed to create a Total Symptom score, defined as the sum of the 6 individual symptom scores other than the inactivity score (each with 0-10 point scale) collected on the same week. The total symptom scale ranges from 0 -60 where higher score indicates a worse level of the condition.
Time Frame	Baseline, Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set (FAS): comprised of all patients who received at least one dose of ruxolitinib.

Arm/Group Title	Ruxolitinib
Arm/Group Description	Ruxolitinib was taken twice daily, unless instructed. Starting dose 15 mg BID for patients with baseline platelet count of 100,000/μL to 200,000/μL (inclusive) or 20 mg BID for those with baseline platelet count >200,000/μL (approximately 12 hours apart: morning and night), increased or decreased per standardized dosing paradigm.
Measure Participants	120
Median (Full Range) [scores on a scale]	-5.0

Adverse Events

Time Frame	Adverse Events are collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All Adverse Events reported in this record are from date of First Patient First Treatment until Last Patient Last Visit up to 240 weeks.
Arm/Group Title	Ruxolitinib
Arm/Group Description	Ruxolitinib was taken twice daily, unless instructed. Starting dose 15 mg BID for patients with baseline platelet count of 100,000/μL to 200,000/μL (inclusive) or 20 mg BID for those with baseline platelet count >200,000/μL (approximately 12 hours apart: morning and night), increased or decreased per standardized dosing paradigm.
All Cause Mortality
	Ruxolitinib
	Affected / at Risk (%)	# Events
Total	13/120 (10.8%)
Serious Adverse Events
	Ruxolitinib
	Affected / at Risk (%)	# Events
Total	60/120 (50%)
Blood and lymphatic system disorders
Anaemia	5/120 (4.2%)
Coagulopathy	1/120 (0.8%)
Disseminated intravascular coagulation	1/120 (0.8%)
Febrile neutropenia	1/120 (0.8%)
Leukocytosis	1/120 (0.8%)
Splenomegaly	1/120 (0.8%)
Cardiac disorders
Cardiac failure	3/120 (2.5%)
Cardiac failure acute	1/120 (0.8%)
Cardiopulmonary failure	1/120 (0.8%)
Myocarditis	1/120 (0.8%)
Pericardial effusion	1/120 (0.8%)
Supraventricular tachycardia	1/120 (0.8%)
Eye disorders
Cataract	1/120 (0.8%)
Glaucoma	1/120 (0.8%)
Gastrointestinal disorders
Abdominal distension	1/120 (0.8%)
Abdominal pain	1/120 (0.8%)
Diarrhoea	1/120 (0.8%)
Enteritis	1/120 (0.8%)
Gastrointestinal haemorrhage	1/120 (0.8%)
Oesophageal varices haemorrhage	1/120 (0.8%)
Upper gastrointestinal haemorrhage	1/120 (0.8%)
Vomiting	1/120 (0.8%)
General disorders
Disuse syndrome	1/120 (0.8%)
Pyrexia	8/120 (6.7%)
Sudden death	1/120 (0.8%)
Hepatobiliary disorders
Bile duct stone	1/120 (0.8%)
Cholecystitis acute	1/120 (0.8%)
Drug-induced liver injury	1/120 (0.8%)
Hepatic function abnormal	1/120 (0.8%)
Hepatorenal syndrome	1/120 (0.8%)
Jaundice	1/120 (0.8%)
Infections and infestations
Abdominal infection	1/120 (0.8%)
Anal abscess	1/120 (0.8%)
Bronchitis	3/120 (2.5%)
Enteritis infectious	1/120 (0.8%)
Gastroenteritis	2/120 (1.7%)
Herpes zoster	6/120 (5%)
Infection	1/120 (0.8%)
Lung infection	6/120 (5%)
Nasopharyngitis	1/120 (0.8%)
Pneumonia	9/120 (7.5%)
Pneumonia bacterial	1/120 (0.8%)
Post procedural infection	1/120 (0.8%)
Pulmonary tuberculosis	1/120 (0.8%)
Respiratory tract infection	1/120 (0.8%)
Sepsis	2/120 (1.7%)
Soft tissue infection	1/120 (0.8%)
Tuberculosis	1/120 (0.8%)
Upper respiratory tract infection	1/120 (0.8%)
Urinary tract infection	1/120 (0.8%)
Injury, poisoning and procedural complications
Ankle fracture	1/120 (0.8%)
Bone contusion	1/120 (0.8%)
Spinal cord injury	1/120 (0.8%)
Thoracic vertebral fracture	1/120 (0.8%)
Investigations
Alanine aminotransferase increased	1/120 (0.8%)
Aspartate aminotransferase increased	1/120 (0.8%)
Bilirubin conjugated increased	1/120 (0.8%)
Blood bilirubin increased	2/120 (1.7%)
Metabolism and nutrition disorders
Hyponatraemia	1/120 (0.8%)
Musculoskeletal and connective tissue disorders
Arthritis	1/120 (0.8%)
Intervertebral disc protrusion	1/120 (0.8%)
Soft tissue mass	1/120 (0.8%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia	1/120 (0.8%)
Blast cell crisis	1/120 (0.8%)
Langerhans' cell histiocytosis	1/120 (0.8%)
Lip squamous cell carcinoma	1/120 (0.8%)
Malignant transformation	1/120 (0.8%)
Nervous system disorders
Dizziness	1/120 (0.8%)
Psychiatric disorders
Depression	1/120 (0.8%)
Renal and urinary disorders
Acute kidney injury	2/120 (1.7%)
Calculus bladder	1/120 (0.8%)
Proteinuria	1/120 (0.8%)
Reproductive system and breast disorders
Cervical dysplasia	1/120 (0.8%)
Respiratory, thoracic and mediastinal disorders
Apnoea	1/120 (0.8%)
Lung disorder	1/120 (0.8%)
Organising pneumonia	1/120 (0.8%)
Pleural effusion	2/120 (1.7%)
Pulmonary embolism	1/120 (0.8%)
Skin and subcutaneous tissue disorders
Neutrophilic dermatosis	1/120 (0.8%)
Skin erosion	1/120 (0.8%)
Vascular disorders
Aortic dissection	1/120 (0.8%)
Deep vein thrombosis	1/120 (0.8%)
Peripheral embolism	1/120 (0.8%)
Other (Not Including Serious) Adverse Events
	Ruxolitinib
	Affected / at Risk (%)	# Events
Total	117/120 (97.5%)
Blood and lymphatic system disorders
Anaemia	87/120 (72.5%)
Leukopenia	7/120 (5.8%)
Neutropenia	11/120 (9.2%)
Thrombocytopenia	34/120 (28.3%)
Gastrointestinal disorders
Abdominal distension	25/120 (20.8%)
Abdominal pain	14/120 (11.7%)
Abdominal pain upper	13/120 (10.8%)
Constipation	21/120 (17.5%)
Diarrhoea	42/120 (35%)
Dyspepsia	8/120 (6.7%)
Nausea	9/120 (7.5%)
Stomatitis	11/120 (9.2%)
Vomiting	9/120 (7.5%)
General disorders
Asthenia	19/120 (15.8%)
Fatigue	12/120 (10%)
Malaise	8/120 (6.7%)
Oedema peripheral	20/120 (16.7%)
Pain	11/120 (9.2%)
Pyrexia	26/120 (21.7%)
Infections and infestations
Herpes zoster	18/120 (15%)
Nasopharyngitis	24/120 (20%)
Upper respiratory tract infection	38/120 (31.7%)
Investigations
Alanine aminotransferase increased	26/120 (21.7%)
Aspartate aminotransferase increased	23/120 (19.2%)
Blood bilirubin increased	9/120 (7.5%)
Blood creatinine increased	10/120 (8.3%)
Blood iron increased	7/120 (5.8%)
Blood urea increased	8/120 (6.7%)
C-reactive protein increased	11/120 (9.2%)
Gamma-glutamyltransferase increased	19/120 (15.8%)
Lymphocyte count decreased	11/120 (9.2%)
Neutrophil count decreased	11/120 (9.2%)
Platelet count decreased	44/120 (36.7%)
Weight increased	15/120 (12.5%)
White blood cell count decreased	8/120 (6.7%)
Metabolism and nutrition disorders
Decreased appetite	10/120 (8.3%)
Hyperkalaemia	7/120 (5.8%)
Hyperuricaemia	17/120 (14.2%)
Hypocalcaemia	9/120 (7.5%)
Iron overload	9/120 (7.5%)
Musculoskeletal and connective tissue disorders
Arthralgia	10/120 (8.3%)
Back pain	10/120 (8.3%)
Musculoskeletal chest pain	11/120 (9.2%)
Myalgia	11/120 (9.2%)
Pain in extremity	12/120 (10%)
Nervous system disorders
Dizziness	13/120 (10.8%)
Headache	16/120 (13.3%)
Psychiatric disorders
Insomnia	14/120 (11.7%)
Respiratory, thoracic and mediastinal disorders
Cough	31/120 (25.8%)
Dyspnoea	8/120 (6.7%)
Epistaxis	9/120 (7.5%)
Productive cough	9/120 (7.5%)
Skin and subcutaneous tissue disorders
Night sweats	13/120 (10.8%)
Pruritus	15/120 (12.5%)
Vascular disorders
Hypertension	13/120 (10.8%)

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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.