COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment: The COMFORT-I Trial

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation
ClinicalTrials.gov Identifier:
NCT00952289
First received: August 4, 2009
Last updated: May 13, 2013
Last verified: May 2013
Results First Received: December 16, 2011  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: Myelofibrosis
Interventions: Drug: Ruxolitinib
Drug: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Ruxolitinib Participants received ruxolitinib orally twice a day. The starting dose was 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 Placebo tablets matching ruxolitinib 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 pre-specified requirements were given the opportunity to crossover to ruxolitinib treatment.

Participant Flow for 2 periods

Period 1:   All Participants
    Ruxolitinib     Placebo  
STARTED     155     154  
Safety Population     155     151 [1]
COMPLETED     134 [2]   114 [3]
NOT COMPLETED     21     40  
Death                 9                 9  
Adverse Event                 8                 8  
Disease progression                 3                 12  
Withdrawal by Subject                 1                 10  
Data lost during site relocation                 0                 1  
[1] Randomized patients who are documented to have received at least 1 dose of study medication.
[2] Represents the number of patients who were still in the study as of 02 November 2010
[3] Includes patients in the study as of 2 November 2010 (78) + those who crossed over to Ruxolitinib.

Period 2:   Patients Who Crossed Over to Ruxolitinib
    Ruxolitinib     Placebo  
STARTED     0     36  
COMPLETED     0     32 [1]
NOT COMPLETED     0     4  
Death                 0                 1  
Withdrawal by Subject                 0                 1  
Non-compliance to study medication                 0                 1  
Physician Decision                 0                 1  
[1] Number of crossover patients who were still in the study as of 02 November 2010



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Ruxolitinib Participants began treatment with ruxolitinib 15 or 20 mg taken orally twice a day based on Baseline platelet count. The dose was adjusted by the Investigator based on efficacy and safety to a maximum of 25 mg twice daily.
Placebo Placebo tablets matching ruxolitinib 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 pre-specified requirements were given the opportunity to crossover to ruxolitinib treatment.
Total Total of all reporting groups

Baseline Measures
    Ruxolitinib     Placebo     Total  
Number of Participants  
[units: participants]
  155     154     309  
Age  
[units: years]
Mean ± Standard Deviation
  66.7  ± 8.82     68.7  ± 8.66     67.7  ± 8.78  
Gender [1]
[units: participants]
     
Female     76     65     141  
Male     79     88     167  
Race/Ethnicity, Customized [2]
[units: participants]
     
Black or African American     6     7     13  
White     138     139     277  
Asian     5     4     9  
Native Hawaiian or Other Pacific Islander     1     0     1  
Other     5     3     8  
Disease Subtype  
[units: participants]
     
Primary myelofibrosis     70     84     154  
Post-polycythemia vera-myelofibrosis     50     47     97  
Post-essential thrombocythemia-myelofibrosis     35     22     57  
Missing     0     1     1  
Spleen volume [3]
[units: cm˄3]
Mean ± Standard Deviation
  2745.7  ± 1247.0     2797.6  ± 1388.5     2771.5  ± 1317.3  
JAK2 V617F Mutation Status [4]
[units: participants]
     
Positive     113     123     236  
Negative     40     27     67  
Unknown/Missing     2     4     6  
[1] Gender data for one patient in the placebo arm was not available because of loss of study data during a move to a new location by the clinical site.
[2] Race data for one patient in the placebo arm was not available because of loss of study data during a move to a new location by the clinical site.
[3] Spleen volume was measured by magnetic resonance imaging or computed tomography scans. Data for one patient in the placebo arm was not available because of loss of study data during a move by the clinical site.
[4] JAK2V617F is a mutation in the pseudokinase domain of Janus Kinase 2 (JAK2) (at amino acid 617, valine to phenylalanine) that results in constitutive activation of JAK2. Mutation status was determined using a validated assay on bone marrow as well as peripheral blood.



  Outcome Measures
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1.  Primary:   Number of Participants Achieving ≥ 35% Reduction in Spleen Volume From Baseline to Week 24   [ Time Frame: Baseline and Week 24 ]

2.  Secondary:   Maintenance of a ≥ 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib   [ Time Frame: Baseline Visit and every 12 weeks until the data cut-off date (up to 14 months). ]

3.  Secondary:   Duration of Maintenance of a ≥ 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib   [ Time Frame: Baseline Visit and every 12 weeks until the data cut-off date (up to 14 months). ]

4.  Secondary:   Number of Participants With a ≥ 50% Reduction in Total Symptom Score From Baseline to Week 24   [ Time Frame: 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. ]

5.  Secondary:   Change From Baseline to Week 24 in Total Symptom Score   [ Time Frame: 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. ]

6.  Secondary:   Overall Survival   [ Time Frame: From randomization to the data cut-off date (up to 14 months). ]

7.  Secondary:   Overall Survival Time   [ Time Frame: From randomization to the data cut-off date (up to 14 months). ]

8.  Secondary:   Overall Survival - Extended Data   [ Time Frame: From randomization to 4 months after the data cut-off date (up to 18 months). ]
  Hide Outcome Measure 8

Measure Type Secondary
Measure Title Overall Survival - Extended Data
Measure Description 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.
Time Frame From randomization to 4 months after the data cut-off date (up to 18 months).  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
ITT population

Reporting Groups
  Description
Ruxolitinib Participants began treatment with ruxolitinib 15 or 20 mg taken orally twice a day based on Baseline platelet count. The dose was adjusted by the Investigator based on efficacy and safety to a maximum of 25 mg twice daily.
Placebo Placebo tablets matching ruxolitinib 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 pre-specified requirements were given the opportunity to crossover to ruxolitinib treatment.

Measured Values
    Ruxolitinib     Placebo  
Number of Participants Analyzed  
[units: participants]
  155     154  
Overall Survival - Extended Data  
[units: participants]
   
Death events     13     24  
Censored events     142     130  

No statistical analysis provided for Overall Survival - Extended Data



9.  Secondary:   Overall Survival Time - Extended Data   [ Time Frame: From randomization to 4 months after the data cut-off date (up to 18 months). ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Study Director
Organization: Incyte Corporation
phone: 855 463-3463


Publications of Results:
Other 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).

Publications automatically indexed to this study:

Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT00952289     History of Changes
Other Study ID Numbers: INCB 18424-351
Study First Received: August 4, 2009
Results First Received: December 16, 2011
Last Updated: May 13, 2013
Health Authority: United States: Food and Drug Administration