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

NCT ID: NCT00952289

Last Updated: 2018-03-12

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

309 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-08-31

Study Completion Date

2015-10-31

Brief Summary

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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).

Detailed Description

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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).

Conditions

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MPN (Myeloproliferative Neoplasms)

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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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).

Group Type EXPERIMENTAL

Ruxolitinib

Intervention Type DRUG

Ruxolitinib phosphate tablets 5 mg administered as oral doses.

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.

Group Type PLACEBO_COMPARATOR

Ruxolitinib

Intervention Type DRUG

Ruxolitinib phosphate tablets 5 mg administered as oral doses.

Placebo

Intervention Type DRUG

Matching placebo tablets were administered as oral doses in the same manner as active drug.

Interventions

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Ruxolitinib

Ruxolitinib phosphate tablets 5 mg administered as oral doses.

Intervention Type DRUG

Placebo

Matching placebo tablets were administered as oral doses in the same manner as active drug.

Intervention Type DRUG

Other Intervention Names

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INCB018424

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Incyte Corporation

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Srdan Verstovsek, MD, PhD

Role: STUDY_DIRECTOR

M.D. Anderson Cancer Center

Locations

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Fullerton, California, United States

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Highland, California, United States

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La Jolla, California, United States

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Los Angeles, California, United States

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Orange, California, United States

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Palo Alto, California, United States

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Panorama City, California, United States

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Rancho Cucamonga, California, United States

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Riverside, California, United States

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Sacramento, California, United States

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San Diego, California, United States

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West Covina, California, United States

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Aurora, Colorado, United States

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Denver, Colorado, United States

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Fort Collins, Colorado, United States

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Norwalk, Connecticut, United States

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Washington D.C., District of Columbia, United States

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Boynton Beach, Florida, United States

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Gainesville, Florida, United States

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Jacksonville, Florida, United States

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West Palm Beach, Florida, United States

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Winter Park, Florida, United States

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Atlanta, Georgia, United States

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Augusta, Georgia, United States

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Honolulu, Hawaii, United States

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Boise, Idaho, United States

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Meridian, Idaho, United States

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Twin Falls, Idaho, United States

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Chicago, Illinois, United States

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Beech Grove, Indiana, United States

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Indianapolis, Indiana, United States

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Ames, Iowa, United States

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Iowa City, Iowa, United States

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Sioux City, Iowa, United States

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Waterloo, Iowa, United States

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Louisville, Kentucky, United States

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Alexandria, Louisiana, United States

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New Orleans, Louisiana, United States

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Baltimore, Maryland, United States

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Ann Arbor, Michigan, United States

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Detroit, Michigan, United States

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Novi, Michigan, United States

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Southfield, Michigan, United States

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Minneapolis, Minnesota, United States

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Rochester, Minnesota, United States

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Saint Louis Park, Minnesota, United States

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New Albany, Mississippi, United States

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St Louis, Missouri, United States

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Billings, Montana, United States

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Denville, New Jersey, United States

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Hackensack, New Jersey, United States

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Morristown, New Jersey, United States

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Somerville, New Jersey, United States

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Albuquerque, New Mexico, United States

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East Setauket, New York, United States

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New York, New York, United States

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Valhalla, New York, United States

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Durham, North Carolina, United States

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Hickory, North Carolina, United States

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Winston-Salem, North Carolina, United States

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Bismarck, North Dakota, United States

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Akron, Ohio, United States

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Canton, Ohio, United States

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Cleveland, Ohio, United States

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Dayton, Ohio, United States

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Dover, Ohio, United States

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Portland, Oregon, United States

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Philadelphia, Pennsylvania, United States

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Pittsburgh, Pennsylvania, United States

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Charleston, South Carolina, United States

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Germantown, Tennessee, United States

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Memphis, Tennessee, United States

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Nashville, Tennessee, United States

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Dallas, Texas, United States

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Houston, Texas, United States

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New Braunfels, Texas, United States

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San Antonio, Texas, United States

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Salt Lake City, Utah, United States

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Burlington, Vermont, United States

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Everett, Washington, United States

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Seattle, Washington, United States

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Milwaukee, Wisconsin, United States

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Darlinghurst, New South Wales, Australia

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Kogarah, New South Wales, Australia

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Randwick, New South Wales, Australia

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St Leonards, New South Wales, Australia

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Brisbane, Queensland, Australia

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Douglas, Queensland, Australia

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Herston, Queensland, Australia

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Milton, Queensland, Australia

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Woolloongabba, Queensland, Australia

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Bedford Park, South Australia, Australia

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Box Hill, Victoria, Australia

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Clayton, Victoria, Australia

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Frankston, Victoria, Australia

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Ringwood East, Victoria, Australia

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Fremantle, Western Australia, Australia

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Perth, Western Australia, Australia

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Vancouver, British Columbia, Canada

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St. John's, Newfoundland and Labrador, Canada

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Halifax, Nova Scotia, Canada

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London, Ontario, Canada

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Ottawa, Ontario, Canada

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Toronto, Ontario, Canada

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Lévis, Quebec, Canada

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Montreal, Quebec, Canada

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Birmingham, Alabama, United States

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Scottsdale, Arizona, United States

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Baldwin Park, California, United States

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Bellflower, California, United States

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Beverly Hills, California, United States

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Corona, California, United States

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Countries

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United States Australia Canada

References

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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).

Reference Type BACKGROUND

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. doi: 10.1056/NEJMoa1110557.

Reference Type RESULT
PMID: 22375971 (View on PubMed)

Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger MW, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner EO, Lyons RM, Paquette R, Raza A, Vaddi K, Erickson-Viitanen S, Sun W, Sandor V, Kantarjian HM. Efficacy, safety and survival with ruxolitinib in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I. Haematologica. 2013 Dec;98(12):1865-71. doi: 10.3324/haematol.2013.092155. Epub 2013 Sep 13.

Reference Type RESULT
PMID: 24038026 (View on PubMed)

Verstovsek S, Mesa RA, Gotlib J, Levy RS, Gupta V, DiPersio JF, Catalano JV, Deininger MW, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner EO, Lyons RM, Raza A, Vaddi K, Sun W, Peng W, Sandor V, Kantarjian H; COMFORT-I investigators. Efficacy, safety, and survival with ruxolitinib in patients with myelofibrosis: results of a median 3-year follow-up of COMFORT-I. Haematologica. 2015 Apr;100(4):479-88. doi: 10.3324/haematol.2014.115840. Epub 2015 Jan 23.

Reference Type RESULT
PMID: 25616577 (View on PubMed)

Verstovsek S, Gotlib J, Mesa RA, Vannucchi AM, Kiladjian JJ, Cervantes F, Harrison CN, Paquette R, Sun W, Naim A, Langmuir P, Dong T, Gopalakrishna P, Gupta V. Long-term survival in patients treated with ruxolitinib for myelofibrosis: COMFORT-I and -II pooled analyses. J Hematol Oncol. 2017 Sep 29;10(1):156. doi: 10.1186/s13045-017-0527-7.

Reference Type DERIVED
PMID: 28962635 (View on PubMed)

Miller CB, Komrokji RS, Mesa RA, Sun W, Montgomery M, Verstovsek S. Practical Measures of Clinical Benefit With Ruxolitinib Therapy: An Exploratory Analysis of COMFORT-I. Clin Lymphoma Myeloma Leuk. 2017 Aug;17(8):479-487. doi: 10.1016/j.clml.2017.05.015. Epub 2017 May 12.

Reference Type DERIVED
PMID: 28606598 (View on PubMed)

Verstovsek S, Mesa RA, Gotlib J, Gupta V, DiPersio JF, Catalano JV, Deininger MW, Miller CB, Silver RT, Talpaz M, Winton EF, Harvey JH Jr, Arcasoy MO, Hexner EO, Lyons RM, Paquette R, Raza A, Jones M, Kornacki D, Sun K, Kantarjian H; COMFORT-I investigators. Long-term treatment with ruxolitinib for patients with myelofibrosis: 5-year update from the randomized, double-blind, placebo-controlled, phase 3 COMFORT-I trial. J Hematol Oncol. 2017 Feb 22;10(1):55. doi: 10.1186/s13045-017-0417-z.

Reference Type DERIVED
PMID: 28228106 (View on PubMed)

Deininger M, Radich J, Burn TC, Huber R, Paranagama D, Verstovsek S. The effect of long-term ruxolitinib treatment on JAK2p.V617F allele burden in patients with myelofibrosis. Blood. 2015 Sep 24;126(13):1551-4. doi: 10.1182/blood-2015-03-635235. Epub 2015 Jul 30.

Reference Type DERIVED
PMID: 26228487 (View on PubMed)

Vannucchi AM, Kantarjian HM, Kiladjian JJ, Gotlib J, Cervantes F, Mesa RA, Sarlis NJ, Peng W, Sandor V, Gopalakrishna P, Hmissi A, Stalbovskaya V, Gupta V, Harrison C, Verstovsek S; COMFORT Investigators. A pooled analysis of overall survival in COMFORT-I and COMFORT-II, 2 randomized phase III trials of ruxolitinib for the treatment of myelofibrosis. Haematologica. 2015 Sep;100(9):1139-45. doi: 10.3324/haematol.2014.119545. Epub 2015 Jun 11.

Reference Type DERIVED
PMID: 26069290 (View on PubMed)

Mesa RA, Verstovsek S, Gupta V, Mascarenhas JO, Atallah E, Burn T, Sun W, Sandor V, Gotlib J. Effects of ruxolitinib treatment on metabolic and nutritional parameters in patients with myelofibrosis from COMFORT-I. Clin Lymphoma Myeloma Leuk. 2015 Apr;15(4):214-221.e1. doi: 10.1016/j.clml.2014.12.008. Epub 2014 Dec 27.

Reference Type DERIVED
PMID: 25682576 (View on PubMed)

Mesa RA, Kiladjian JJ, Verstovsek S, Al-Ali HK, Gotlib J, Gisslinger H, Levy R, Siulnik A, Gupta V, Khan M, DiPersio JF, McQuitty M, Catalano JV, Hunter DS, Knoops L, Deininger M, Cervantes F, Miller C, Vannucchi AM, Silver RT, Barbui T, Talpaz M, Barosi G, Winton EF, Mendeson E, Harvey JH Jr, Arcasoy MO, Hexner E, Lyons RM, Paquette R, Raza A, Sun W, Sandor V, Kantarjian HM, Harrison C. Comparison of placebo and best available therapy for the treatment of myelofibrosis in the phase 3 COMFORT studies. Haematologica. 2014 Feb;99(2):292-8. doi: 10.3324/haematol.2013.087650. Epub 2013 Aug 2.

Reference Type DERIVED
PMID: 23911705 (View on PubMed)

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.

Reference Type DERIVED
PMID: 23423753 (View on PubMed)

Other Identifiers

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INCB 18424-351

Identifier Type: -

Identifier Source: org_study_id

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