Controlled Myelofibrosis Study With Oral Janus-associated Kinase (JAK) Inhibitor Treatment-II: The COMFORT-II Trial

NCT00934544 | Completed Phase 3 Results DMC

• 3 other identifiers: CINC424A2352CINCB 18424-3522009-009858-24
• Study Type: interventional
• Target: 219
• Locations: 9 countries
• Sites: 61

Brief Summary

This was an open label, randomized study comparing the efficacy and safety of randomized 2:1 Ruxolitinib tablets versus best-available therapy, as selected by the investigator. The purpose was to compare the efficacy, safety and tolerability of Ruxolitinib (INC424/INCB018424) given twice daily to the best-available therapy, in subjects with primary myelofibrosis (PMF), post polycythemia vera myelofibrosis (PPV-MF) or post essential thrombocythemia myelofibrosis (PET-MF).

Conditions

Myelofibrosis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 48

  The change in spleen volume from baseline to week 48 was measured by magnetic resonance imaging (MRI) (or by computer tomography (CT) for participants unable to undergo MRI) and was calculated only for participants who had an evaluable spleen volume at baseline. The percentage of participants achieving a greater than or equal to 35% reduction in spleen volume from baseline to week 48 was then calculated by treatment group.

  Baseline, Week 48

Secondary Outcomes (10)

• Duration of Maintenance of Spleen Volume Reduction (Median)

  Baseline, up to Year 5

• Duration of Maintenance of Spleen Volume Reduction (Kaplan-Meier Estimates)

  Baseline, up to Year 5

• Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24

  Baseline, Week 24

• Time to First at Least 35% Reduction in Spleen Volume From Baseline by Treatment (Primary Analysis)

  Time from randomization and date of the first MRI showing at least 35% reduction from baseline in spleen volume

• Progression-free Survival (PFS)

  Time from randomization and the earliest of either increase in spleen volume >=25% from on-study nadir, splenic irradiation, splenectomy, leukemic transformation or death

Study Arms (2)

Ruxolitinib

EXPERIMENTAL

5 mg tablets administered orally in an outpatient setting according to the protocol-specified dosing schedule

Drug: Ruxolitinib

Best Available Therapy (BAT)

ACTIVE COMPARATOR

Commercially available therapy, oral or parenteral, per manufacturer's instructions and Investigator discretion. BAT included the option of no treatment. Patients randomized to BAT were eligible to cross over to receive open-label ruxolitinib after a qualifying progression event, if they met the safety criteria. After the primary analysis in January 2011, patients randomized to receive BAT were allowed to cross over to receive ruxolitinib and move to the extension phase of the study without a qualifying progression event.

Drug: Best Available Therapy (BAT)

Interventions

Ruxolitinib DRUG

5 mg tablets packaged as 60-count in high-density polyethylene bottles

Ruxolitinib

Best Available Therapy (BAT) DRUG

Prescribing and usage per respective package inserts

Best Available Therapy (BAT)

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 PMF, PPV-MF or PET-MF according to the 2008 World Health Organization criteria
• Subjects with MF 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 ECOG performance status of 0, 1, 2 or 3
• Subjects with peripheral blood blast count of \< 10%.
• Subjects who have not previously received treatment with a 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 any history of platelet counts \< 50,000/µL or ANC \< 500/µL except during treatment for a myeloproliferative disorder or treatment with cytotoxic therapy for any other reason
• 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

• Novartis Pharmaceuticals: lead

Study Sites (61)

Novartis Investigative Site

Innsbruck, 6020, Austria

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Novartis Investigative Site

Linz, 4010, Austria

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Novartis Investigative Site

Salzburg, 5020, Austria

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Novartis Investigative Site

Vienna, A-1090, Austria

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Novartis Investigative Site

Antwerp, 2020, Belgium

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Novartis Investigative Site

Antwerp, 2060, Belgium

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Novartis Investigative Site

Bruges, 8000, Belgium

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Novartis Investigative Site

Brussels, 1200, Belgium

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Novartis Investigative Site

Hasselt, 3500, Belgium

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Novartis Investigative Site

Kortrijk, 8500, Belgium

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Novartis Investigative Site

La Louvière, 7100, Belgium

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Novartis Investigative Site

Leuven, 3000, Belgium

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Novartis Investigative Site

Roeselare, 8800, Belgium

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Novartis Investigative Site

Yvoir, 5530, Belgium

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Novartis Investigative Site

Amiens, 80054, France

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Novartis Investigative Site

Caen, 14033, France

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Novartis Investigative Site

Grenoble, 38043, France

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Novartis Investigative Site

Lens, 62307, France

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Novartis Investigative Site

Lille, 59037, France

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Novartis Investigative Site

Lyon, 69437, France

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Novartis Investigative Site

Marseille, 13273, France

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Novartis Investigative Site

Nîmes, 30029, France

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Novartis Investigative Site

Paris, 75010, France

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Novartis Investigative Site

Paris, 75012, France

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Novartis Investigative Site

Paris, 75014, France

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Novartis Investigative Site

Pessac, 33600, France

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Novartis Investigative Site

Poitiers, 86021, France

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Novartis Investigative Site

Rennes, F-35043, France

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Novartis Investigative Site

Strasbourg, 67091, France

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Novartis Investigative Site

Toulouse, 31059, France

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Novartis Investigative Site

Villejuif, 94805, France

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Novartis Investigative Site

Berlin, 13353, Germany

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Novartis Investigative Site

Cologne, 50937, Germany

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Novartis Investigative Site

Frankfurt/M, 60590, Germany

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Novartis Investigative Site

Magdeburg, 39120, Germany

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Novartis Investigative Site

Mainz, 55131, Germany

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Novartis Investigative Site

Münster, 48149, Germany

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Novartis Investigative Site

Stuttgart, 70376, Germany

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Novartis Investigative Site

Tübingen, 72076, Germany

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Novartis Investigative Site

Ulm, 89081, Germany

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Novartis Investigative Site

Pavia, (PV), 27100, Italy

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Novartis Investigative Site

Monza, MB, 20900, Italy

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Novartis Investigative Site

Milan, MI, 20162, Italy

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Novartis Investigative Site

Florence, 50134, Italy

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Novartis Investigative Site

Orbassano, 10043, Italy

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Novartis Investigative Site

Pavia, 27100, Italy

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Novartis Investigative Site

Amsterdam, 1081, Netherlands

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Novartis Investigative Site

Groningen, 9713 GZ, Netherlands

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Novartis Investigative Site

Maastricht, 5800, Netherlands

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Novartis Investigative Site

Nijmegen, 6500 MB, Netherlands

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Novartis Investigative Site

Rotterdam, 3015 CE, Netherlands

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Novartis Investigative Site

The Hague, 2545 CH, Netherlands

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Novartis Investigative Site

Barcelona, Catalonia, 08036, Spain

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Novartis Investigative Site

Majadahonda, Madrid, 28222, Spain

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Novartis Investigative Site

Valencia, Valencia, 46010, Spain

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Novartis Investigative Site

Gothenburg, SE-413 45, Sweden

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Novartis Investigative Site

Stockholm, SE-118 83, Sweden

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Novartis Investigative Site

Belfast, BT9 7AB, United Kingdom

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Novartis Investigative Site

Cambridge, CB2 2QQ, United Kingdom

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Novartis Investigative Site

London, SE1 9RT, United Kingdom

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Novartis Investigative Site

Oxford, OX37LJ, United Kingdom

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Related Publications (7)

• 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

• McMullin MF, Harrison CN, Niederwieser D, Demuynck H, Jakel N, Gopalakrishna P, McQuitty M, Stalbovskaya V, Recher C, Theunissen K, Gisslinger H, Kiladjian JJ, Al-Ali HK. The use of erythropoiesis-stimulating agents with ruxolitinib in patients with myelofibrosis in COMFORT-II: an open-label, phase 3 study assessing efficacy and safety of ruxolitinib versus best available therapy in the treatment of myelofibrosis. Exp Hematol Oncol. 2015 Sep 15;4:26. doi: 10.1186/s40164-015-0021-2. eCollection 2015.

  PMID: 26380150 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

• Cervantes F, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Sirulnik A, Stalbovskaya V, McQuitty M, Hunter DS, Levy RS, Passamonti F, Barbui T, Barosi G, Harrison CN, Knoops L, Gisslinger H; COMFORT-II investigators. Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Blood. 2013 Dec 12;122(25):4047-53. doi: 10.1182/blood-2013-02-485888. Epub 2013 Oct 30.

  PMID: 24174625 DERIVED

• Wilkins BS, Radia D, Woodley C, Farhi SE, Keohane C, Harrison CN. Resolution of bone marrow fibrosis in a patient receiving JAK1/JAK2 inhibitor treatment with ruxolitinib. Haematologica. 2013 Dec;98(12):1872-6. doi: 10.3324/haematol.2013.095109. Epub 2013 Sep 20.

  PMID: 24056820 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

• Harrison C, Kiladjian JJ, Al-Ali HK, Gisslinger H, Waltzman R, Stalbovskaya V, McQuitty M, Hunter DS, Levy R, Knoops L, Cervantes F, Vannucchi AM, Barbui T, Barosi G. JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. N Engl J Med. 2012 Mar 1;366(9):787-98. doi: 10.1056/NEJMoa1110556.

  PMID: 22375970 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis

Interventions

ruxolitinib

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Results Point of Contact

• Title: Clinical Disclosure Office
• Organization: Novartis Pharmaceuticals

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  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: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2009
• First Posted: July 8, 2009
• Study Start: July 1, 2009
• Primary Completion: March 4, 2015
• Study Completion: March 4, 2015
• Last Updated: August 19, 2019
• Results First Posted: May 30, 2012

Record last verified: 2019-07

Locations

DE (9); SE (2); NL (6); GB (4); FR (17); IT (6); AU (4); ES (3); BE (10)