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

History of Changes

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
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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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.

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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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 ]

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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). ]

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Measure Type	Secondary
Measure Title	Maintenance of a ≥ 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib
Measure Description	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. Observed events represents the number of patients who lost the response prior to the data cutoff date and Censored events is the number who were still responding at the time of the data cutoff.
Time Frame	Baseline Visit and every 12 weeks until the data cut-off date (up to 14 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.
Patients who had at least 1 measurement of ≥ 35% reduction from Baseline in spleen volume at any time during the study and had at least 1 subsequent measurement or withdrew prior to another assessment.

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.

Measured Values

	Ruxolitinib
Number of Participants Analyzed [units: participants]	71
Maintenance of a ≥ 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib [units: participants]
Observed Events	19
Censored Events	52

No statistical analysis provided for Maintenance of a ≥ 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib

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). ]

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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. ]

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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. ]

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6. Secondary:

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

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7. Secondary:

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

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8. Secondary:

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

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9. Secondary:

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

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Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Following the first publication, the Institution and/or Principal Investigator may publish data or results from the Study, provided, however, that the Institution and/or Principal Investigator submits the proposed publication to the Sponsor for review at least sixty (60) days prior to the date of the proposed publication. Sponsor may remove from the proposed publication any information that is considered confidential and/or proprietary other than Study data and results.

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:

Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger M, Miller C, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Koumenis IL, Sun W, Sandor V, Kantarjian HM. A double-blind, placebo-controlled trial of ruxolitinib for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):799-807.

Publications automatically indexed to this study:

Mesa RA, Gotlib J, Gupta V, Catalano JV, Deininger MW, Shields AL, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH, Hare T, Erickson-Viitanen S, Sun W, Sandor V, Levy RS, Kantarjian HM, Verstovsek S. Effect of ruxolitinib therapy on myelofibrosis-related symptoms and other patient-reported outcomes in COMFORT-I: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 2013 Apr 1;31(10):1285-92. doi: 10.1200/JCO.2012.44.4489. Epub 2013 Feb 19.

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

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