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

February 12, 2018 updated by: Incyte Corporation

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients with spleen growth of greater than 25% based on an increase in spleen volume from Baseline were eligible for early unblinding, and for patients on placebo, cross over to ruxolitinib prior to the primary study endpoint being reached. If this spleen growth occurred before Week 24, it must have been accompanied by specific worsening of symptoms, based on worsening early satiety accompanied by weight loss or worsening pain requiring daily narcotic use. After Week 24, asymptomatic spleen growth alone was sufficient for early unblinding and potential cross over. Patients found to have been randomized to ruxolitinib after early unblinding prior to Week 24 were discontinued.

When half of the patients remaining in the study completed the Week 36 visit and all patients enrolled completed Week 24 or discontinued, the database was frozen and the primary analysis was conducted. Once this was complete, all patients were unblinded and patients who had been randomized to placebo were given the opportunity to cross over to ruxolitinib treatment, provided hematology laboratory parameters were adequate; 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).

Study Type

Interventional

Enrollment (Actual)

309

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • New South Wales
      • Darlinghurst, New South Wales, Australia
      • Kogarah, New South Wales, Australia
      • Randwick, New South Wales, Australia
      • St Leonards, New South Wales, Australia
    • Queensland
      • Brisbane, Queensland, Australia
      • Douglas, Queensland, Australia
      • Herston, Queensland, Australia
      • Milton, Queensland, Australia
      • Woolloongabba, Queensland, Australia
    • South Australia
      • Bedford Park, South Australia, Australia
    • Victoria
      • Box Hill, Victoria, Australia
      • Clayton, Victoria, Australia
      • Frankston, Victoria, Australia
      • Ringwood East, Victoria, Australia
    • Western Australia
      • Fremantle, Western Australia, Australia
      • Perth, Western Australia, Australia
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada
    • Newfoundland and Labrador
      • St. John's, Newfoundland and Labrador, Canada
    • Nova Scotia
      • Halifax, Nova Scotia, Canada
    • Ontario
      • London, Ontario, Canada
      • Ottawa, Ontario, Canada
      • Toronto, Ontario, Canada
    • Quebec
      • Levis, Quebec, Canada
      • Montreal, Quebec, Canada
  • United States
    • Alabama
      • Birmingham, Alabama, United States
    • Arizona
      • Scottsdale, Arizona, United States
    • California
      • Baldwin Park, California, United States
      • Bellflower, California, United States
      • Beverly Hills, California, United States
      • Corona, California, United States
      • Fullerton, California, United States
      • Highland, California, United States
      • La Jolla, California, United States
      • Los Angeles, California, United States
      • Orange, California, United States
      • Palo Alto, California, United States
      • Panorama City, California, United States
      • Rancho Cucamonga, California, United States
      • Riverside, California, United States
      • Sacramento, California, United States
      • San Diego, California, United States
      • West Covina, California, United States
    • Colorado
      • Aurora, Colorado, United States
      • Denver, Colorado, United States
      • Fort Collins, Colorado, United States
    • Connecticut
      • Norwalk, Connecticut, United States
    • District of Columbia
      • Washington, District of Columbia, United States
    • Florida
      • Boynton Beach, Florida, United States
      • Gainesville, Florida, United States
      • Jacksonville, Florida, United States
      • West Palm Beach, Florida, United States
      • Winter Park, Florida, United States
    • Georgia
      • Atlanta, Georgia, United States
      • Augusta, Georgia, United States
    • Hawaii
      • Honolulu, Hawaii, United States
    • Idaho
      • Boise, Idaho, United States
      • Meridian, Idaho, United States
      • Twin Falls, Idaho, United States
    • Illinois
      • Chicago, Illinois, United States
    • Indiana
      • Beech Grove, Indiana, United States
      • Indianapolis, Indiana, United States
    • Iowa
      • Ames, Iowa, United States
      • Iowa City, Iowa, United States
      • Sioux City, Iowa, United States
      • Waterloo, Iowa, United States
    • Kentucky
      • Louisville, Kentucky, United States
    • Louisiana
      • Alexandria, Louisiana, United States
      • New Orleans, Louisiana, United States
    • Maryland
      • Baltimore, Maryland, United States
    • Michigan
      • Ann Arbor, Michigan, United States
      • Detroit, Michigan, United States
      • Novi, Michigan, United States
      • Southfield, Michigan, United States
    • Minnesota
      • Minneapolis, Minnesota, United States
      • Rochester, Minnesota, United States
      • Saint Louis Park, Minnesota, United States
    • Mississippi
      • New Albany, Mississippi, United States
    • Missouri
      • Saint Louis, Missouri, United States
    • Montana
      • Billings, Montana, United States
    • New Jersey
      • Denville, New Jersey, United States
      • Hackensack, New Jersey, United States
      • Morristown, New Jersey, United States
      • Somerville, New Jersey, United States
    • New Mexico
      • Albuquerque, New Mexico, United States
    • New York
      • East Setauket, New York, United States
      • New York, New York, United States
      • Valhalla, New York, United States
    • North Carolina
      • Durham, North Carolina, United States
      • Hickory, North Carolina, United States
      • Winston-Salem, North Carolina, United States
    • North Dakota
      • Bismarck, North Dakota, United States
    • Ohio
      • Akron, Ohio, United States
      • Canton, Ohio, United States
      • Cleveland, Ohio, United States
      • Dayton, Ohio, United States
      • Dover, Ohio, United States
    • Oregon
      • Portland, Oregon, United States
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
      • Pittsburgh, Pennsylvania, United States
    • South Carolina
      • Charleston, South Carolina, United States
    • Tennessee
      • Germantown, Tennessee, United States
      • Memphis, Tennessee, United States
      • Nashville, Tennessee, United States
    • Texas
      • Dallas, Texas, United States
      • Houston, Texas, United States
      • New Braunfels, Texas, United States
      • San Antonio, Texas, United States
    • Utah
      • Salt Lake City, Utah, United States
    • Vermont
      • Burlington, Vermont, United States
    • Washington
      • Everett, Washington, United States
      • Seattle, Washington, United States
    • Wisconsin
      • Milwaukee, Wisconsin, United States

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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).
Drug: Ruxolitinib
Ruxolitinib phosphate tablets 5 mg administered as oral doses.
Other Names:
  • INCB018424
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.
Drug: Ruxolitinib
Ruxolitinib phosphate tablets 5 mg administered as oral doses.
Other Names:
  • INCB018424
Drug: Placebo
Matching placebo tablets were administered as oral doses in the same manner as active drug.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants Achieving ≥ 35% Reduction in Spleen Volume From Baseline to Week 24
Time Frame: Baseline and Week 24
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.
Baseline and Week 24

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
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.
Baseline Visit and every 12 weeks until the data cut-off date (up to 14 months).
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).
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.
Baseline Visit and every 12 weeks until the data cut-off date (up to 14 months).
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.
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.
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.
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.
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.
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.
Overall Survival
Time Frame: From randomization to the data cut-off date (up to 14 months).
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.
From randomization to the data cut-off date (up to 14 months).
Overall Survival Time
Time Frame: From randomization to the data cut-off date (up to 14 months).
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.
From randomization to the data cut-off date (up to 14 months).
Overall Survival - Extended Data
Time Frame: From randomization to 4 months after the data cut-off date (up to 18 months).
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.
From randomization to 4 months after the data cut-off date (up to 18 months).
Overall Survival Time - Extended Data
Time Frame: From randomization to 4 months after the data cut-off date (up to 18 months).
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.
From randomization to 4 months after the data cut-off date (up to 18 months).
Overall Survival at Week 144
Time Frame: Week 144
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.
Week 144
Overall Survival Time at Week 144
Time Frame: Week 144
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.
Week 144

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Incyte Corporation

Investigators

  • Study Director: Srdan Verstovsek, MD, PhD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2009

Primary Completion (ACTUAL)

November 1, 2010

Study Completion (ACTUAL)

October 1, 2015

Study Registration Dates

First Submitted

August 4, 2009

First Submitted That Met QC Criteria

August 5, 2009

First Posted (ESTIMATE)

August 6, 2009

Study Record Updates

Last Update Posted (ACTUAL)

March 12, 2018

Last Update Submitted That Met QC Criteria

February 12, 2018

Last Verified

February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INCB 18424-351

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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