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

NCT00952289 | Completed Phase 3 Results DMC

• 1 other identifier: INCB 18424-351
• Study Type: interventional
• Target: 309
• Locations: 3 countries
• Sites: 112

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).

Conditions

MPN (Myeloproliferative Neoplasms)

Keywords

Myelofibrosis; Post-Polycythemia Vera Myelofibrosis; Post-Essential Thrombocythemia Myelofibrosis

Outcome Measures

Primary Outcomes (1)

• Number of Participants Achieving ≥ 35% Reduction in Spleen Volume From Baseline to 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 Outcomes (10)

• Maintenance of a ≥ 35% Reduction From Baseline in Spleen Volume Among Patients Initially Randomized to Receive Ruxolitinib

  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

  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

  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

  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

  From randomization to the data cut-off date (up to 14 months).

Study Arms (2)

Ruxolitinib

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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; Drug: Placebo

Interventions

Ruxolitinib DRUG

Ruxolitinib phosphate tablets 5 mg administered as oral doses.

Also known as: INCB018424

Placebo; Ruxolitinib

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (112)

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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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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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Related Publications (12)

• 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).

  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.

  PMID: 22375971 RESULT

• 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.

  PMID: 24038026 RESULT

• 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.

  PMID: 25616577 RESULT

• 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.

  PMID: 28962635 DERIVED

• 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.

  PMID: 28606598 DERIVED

• 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.

  PMID: 28228106 DERIVED

• 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.

  PMID: 26228487 DERIVED

• 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.

  PMID: 26069290 DERIVED

• 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.

  PMID: 25682576 DERIVED

• 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.

  PMID: 23911705 DERIVED

• 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.

  PMID: 23423753 DERIVED

MeSH Terms

Conditions

Myeloproliferative Disorders; Primary Myelofibrosis

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Study Director
• Organization: Incyte Corporation

855 463-3463

Study Officials

• Srdan Verstovsek, MD, PhD

  M.D. Anderson Cancer Center

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2009
• First Posted: August 6, 2009
• Study Start: August 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: October 1, 2015
• Last Updated: March 12, 2018
• Results First Posted: January 24, 2012

Record last verified: 2018-02

Locations

AU (16); US (88); CA (8)