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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT00952289
Registration number
NCT00952289
Ethics application status
Date submitted
4/08/2009
Date registered
6/08/2009
Date last updated
12/03/2018
Titles & IDs
Public title
COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment: The COMFORT-I Trial
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Scientific title
A Randomized, Double-blind, Placebo-controlled Study of the JAK Inhibitor INCB018424 Tablets Administered Orally to Subjects With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis or Post-Essential Thrombocythemia Myelofibrosis
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Secondary ID [1]
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INCB 18424-351
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
MPN (Myeloproliferative Neoplasms)
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Condition category
Condition code
Blood
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Haematological diseases
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Blood
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Other blood disorders
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Musculoskeletal
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Other muscular and skeletal disorders
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Human Genetics and Inherited Disorders
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Other human genetics and inherited disorders
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Cancer
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Leukaemia - Chronic leukaemia
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Cancer
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Leukaemia - Acute leukaemia
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Ruxolitinib
Treatment: Drugs - Placebo
Experimental: Ruxolitinib - Participants received ruxolitinib orally twice a day. The starting dose was determined based on Baseline platelet count. Patients with Baseline platelet count > 200,000/µL began a dose regimen of 20 mg twice daily. Patients with Baseline platelet count of 100,000/µL to 200,000/µL (inclusive) began a dose regimen of 15 mg twice daily. The dose was adjusted by the Investigator based on efficacy and safety to a maximum of 25 mg twice daily. Patients receiving benefit could continue treatment until the later of marketing approval or when the last randomized patient remaining in the study had completed Week 144 (36 months).
Placebo Comparator: Placebo - Placebo tablets matching ruxolitinib were administered orally twice a day at a starting dose based on Baseline platelet count. Doses were titrated using the same guidelines as for active drug. Patients meeting certain protocol requirements detailed below were given the opportunity to cross over to ruxolitinib treatment.
Treatment: Drugs: Ruxolitinib
Ruxolitinib phosphate tablets 5 mg administered as oral doses.
Treatment: Drugs: Placebo
Matching placebo tablets were administered as oral doses in the same manner as active drug.
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Number of Participants Achieving = 35% Reduction in Spleen Volume From Baseline to Week 24
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Assessment method [1]
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Spleen volume was assessed by magnetic resonance imaging (MRI) or by computed tomography (CT) scans if MRI was not suitable, and analyzed by a blinded central laboratory reader. Patients who withdrew, crossed over to ruxolitinib prior to the visit, or had a missing value at the visit were considered non-responders.
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Timepoint [1]
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Baseline and Week 24
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Secondary outcome [1]
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Maintenance of a = 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib
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Assessment method [1]
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The maintenance of = 35% reduction from Baseline in spleen volume was assessed up until the data cutoff date using the Kaplan-Meier method for patients who had at least one measured = 35% reduction, and who either had at least one subsequent measurement or who subsequently dropped out prior to another assessment.
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Timepoint [1]
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Baseline Visit and every 12 weeks until the data cut-off date (up to 14 months).
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Secondary outcome [2]
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Duration of Maintenance of a = 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib
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Assessment method [2]
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The duration of = 35% reduction from Baseline in spleen volume was defined as the longest duration of consecutive measurements of = 35% reduction observed before the data cut-off date for patients who had at least one measured = 35% reduction, and who either had at least one subsequent measurement or, who subsequently dropped out prior to another assessment. The duration of a = 35% reduction from Baseline in spleen volume was analyzed using the Kaplan-Meier method.
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Timepoint [2]
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Baseline Visit and every 12 weeks until the data cut-off date (up to 14 months).
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Secondary outcome [3]
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Number of Participants With a = 50% Reduction in Total Symptom Score From Baseline to Week 24
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Assessment method [3]
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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.
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Timepoint [3]
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Baseline and Week 24. Baseline total score was the average of the daily total scores for the last 7 days prior to randomization. The Week 24 total score was the average of daily total scores from the 28 days prior to the Week 24 visit.
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Secondary outcome [4]
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Change From Baseline to Week 24 in Total Symptom Score
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Assessment method [4]
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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 hence a negative change from baseline indicates improvement.
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Timepoint [4]
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Baseline and Week 24. Baseline total score was the average of the daily total scores for the last 7 days prior to randomization. The Week 24 total score was the average of daily total scores from the 28 days prior to the Week 24 visit.
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Secondary outcome [5]
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Overall Survival
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Assessment method [5]
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Overall survival is reported here by the number of deaths from randomization until the data cut-off. Patients were censored at the time of database cut-off or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of data cut. The survival time was analyzed using the Kaplan-Meier method.
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Timepoint [5]
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From randomization to the data cut-off date (up to 14 months).
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Secondary outcome [6]
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Overall Survival Time
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Assessment method [6]
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Overall survival was assessed by the time to death or censoring. Patients were censored at the time of database cut-off or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of data cut. The survival time was analyzed using the Kaplan-Meier method.
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Timepoint [6]
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From randomization to the data cut-off date (up to 14 months).
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Secondary outcome [7]
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Overall Survival - Extended Data
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Assessment method [7]
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Overall survival is reported here by the number of deaths from randomization until 01 March 2011. Patients were censored at this time or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of data cut. The survival time was analyzed using the Kaplan-Meier method. This outcome reports data from August 2009 through March 2011 to coincide with a pre-planned New Drug Application (NDA) 120-day safety update.
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Timepoint [7]
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From randomization to 4 months after the data cut-off date (up to 18 months).
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Secondary outcome [8]
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Overall Survival Time - Extended Data
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Assessment method [8]
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Overall survival was assessed by the time to death or censoring up until 01 March 2011. Patients were censored at this time or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of data cut. The survival time was analyzed using the Kaplan-Meier method. This outcome reports data from August 2009 through March 2011 to coincide with a pre-planned New Drug Application (NDA) 120-day safety update.
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Timepoint [8]
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From randomization to 4 months after the data cut-off date (up to 18 months).
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Secondary outcome [9]
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Overall Survival at Week 144
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Assessment method [9]
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Overall survival is reported here by the number of deaths from randomization until the data cut-off. Patients were censored at the time of database cut-off or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of database cut-off. The survival time was analyzed using the Kaplan-Meier method.
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Timepoint [9]
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Week 144
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Secondary outcome [10]
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Overall Survival Time at Week 144
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Assessment method [10]
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Overall survival was assessed by the time to death or censoring. Patients were censored at the time of database cut-off or the later of either the date of withdrawal or the date of last follow-up for patients who withdrew from study before the date of database cut-off. The survival time was analyzed using the Kaplan-Meier method.
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Timepoint [10]
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Week 144
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Eligibility
Key inclusion criteria
- Subjects must be diagnosed with primary myelofibrosis (PMF), post-polycythemia
vera-myelofibrosis (PPV-MF) or post-essential thrombocythemia-myelofibrosis (PET-MF)
according to the 2008 World Health Organization criteria
- Subjects with myelofibrosis 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 Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1,
2 or 3
- Subjects who have not previously received treatment with a Janus kinase (JAK)
inhibitor
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key 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 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
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 3
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Completed
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
1/08/2009
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
1/10/2015
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Sample size
Target
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Accrual to date
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Final
309
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Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
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Recruitment hospital [1]
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- Darlinghurst
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Recruitment hospital [2]
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- Kogarah
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- Randwick
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- St Leonards
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- Brisbane
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Recruitment hospital [6]
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- Douglas
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Recruitment hospital [7]
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- Herston
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Recruitment hospital [8]
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- Milton
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Recruitment hospital [9]
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- Woolloongabba
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Recruitment hospital [10]
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- Bedford Park
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Recruitment hospital [11]
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- Box Hill
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Recruitment hospital [12]
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- Clayton
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Recruitment hospital [13]
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- Frankston
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Recruitment hospital [14]
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- Ringwood East
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- Fremantle
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- Perth
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- Darlinghurst
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- Kogarah
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- Randwick
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- St Leonards
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- Brisbane
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- Douglas
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- Herston
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- Milton
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- Woolloongabba
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- Bedford Park
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- Box Hill
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- Clayton
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- Frankston
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- Ringwood East
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- Fremantle
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- Perth
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Recruitment outside Australia
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Alabama
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Incyte Corporation
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Address
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Ethics approval
Ethics application status
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Summary
Brief summary
This was a randomized, double-blind study comparing the efficacy and safety of ruxolitinib
(INCB018424) tablets to matching placebo tablets in patients diagnosed with Myelofibrosis
(either Primary Myelofibrosis (PMF) or Post-Polycythemia Vera Myelofibrosis (PPV-MF) or
Post-Essential Thrombocythemia Myelofibrosis (PET-MF).
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Trial website
https://clinicaltrials.gov/ct2/show/NCT00952289
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Trial related presentations / publications
Verstovsek S, Mesa R, Gotlib J, et al. Results of COMFORT-I, a randomized double-blind phase III trial of JAK1/2 inhibitor INCB18424 (424) vs placebo (PB) for patients with myelofibrosis (MF). The 47th Annual ASCO meeting, Chicago, IL. J Clin Oncol 2011; 29 (suppl; abstract 6500). Verstovsek S, Mesa R, Gotlib J, et al. Results of COMFORT-I, a randomized, double-blind phase III trial of the JAK1 and JAK2 inhibitor ruxolitinib (INCB018424) versus placebo for patients with myelofibrosis. The 16th Annual EHA meeting, London, UK. Haematologica 2011; 96 (suppl 2; abstract 0505).
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Public notes
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Contacts
Principal investigator
Name
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Srdan Verstovsek, MD, PhD
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Address
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M.D. Anderson Cancer Center
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT00952289
Download to PDF