Combination of JAK2 Inhibitor and Erythropoiesis-stimulating Agent in Myelofibrosis

NCT03208803 | Completed

• 1 other identifier: 15-10_Ruxo-EPO
• Study Type: observational
• Target: 65
• Locations: 0 countries
• Sites: N/A

Brief Summary

In patients with myelofibrosis, ruxolitinib is a current therapeutic option, which has demonstrated rapid and durable reduction in splenomegaly and improved disease-related symptoms. Anemia is another frequent issue in myelofibrosis. Consistent with its JAK2 signalling inhibition, ruxolitinib therapy has been shown to be detrimental on the hemoglobin level, increasing the depth of anemia or transfusion need. Despite potential antagonistic mechanisms of action on Janus Kinase 2, some responses on anemia have been reported with the addition of Erythropoiesis-stimulating Agent to ruxolitinib in a small subset of patients in the COMFORT II study. Ruxo-EPO is an observational study aimed to better assess the combination of Erythropoiesis-stimulating Agent and a Janus Kinase 2 inhibitor for therapeutic efficacy on anemia, Myelofibrosis evolution and for tolerance, in a larger cohort of patients treated for myelofibrosis in general practice.

Conditions

Myelofibrosis; Anemia

Keywords

Myelofibrosis; Erythropoiesis-stimulating Agents; Janus Kinase 2 inhibitors; Ruxolitinib

Outcome Measures

Primary Outcomes (1)

• Effect on anemia of the combination Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent

  Response rate assessed with 2006 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Network (ELN) criteria

  6 months

Secondary Outcomes (8)

• Patterns of the combination Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent

  6 months

• Patients and Myelofibrosis characteristics

  at inclusion

• Response rate of the combination treatment on constitutional symptoms of myelofibrosis

  3 years

• Response rate of the combination treatment on splenomegaly

  3 years

• Efficacy of the combination treatment on bone marrow fibrosis

  3 years

Eligibility Criteria

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

Study Population

Patients with myelofibroses treated with a combination of Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent in one of the France Intergroup Myeloproliferative neoplasms centers

You may qualify if:

• patients with primary myelofibrosis or post-polycythemia myelofibrosis or post-essential thrombocythemia myelofibrosis
• previously started with a combination of Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent, whatever the date during the course of their disease

You may not qualify if:

• \- patients who denied participating to this observational study

Sponsors & Collaborators

• Centre Hospitalier Annecy Genevois: lead

Related Publications (7)

• Cervantes F. How I treat myelofibrosis. Blood. 2014 Oct 23;124(17):2635-42. doi: 10.1182/blood-2014-07-575373. Epub 2014 Sep 16.

  PMID: 25232060 BACKGROUND

• James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, Garcon L, Raslova H, Berger R, Bennaceur-Griscelli A, Villeval JL, Constantinescu SN, Casadevall N, Vainchenker W. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005 Apr 28;434(7037):1144-8. doi: 10.1038/nature03546.

  PMID: 15793561 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Ellis MH, Lavi N, Mishchenko E, Dally N, Lavie D, Courevitch A, Gutwein O, Bulvik S, Braester A, Chubar E, Tavor S, Duek A, Kirgner I, Koren-Michowitz M. Ruxolitinib treatment for myelofibrosis: Efficacy and tolerability in routine practice. Leuk Res. 2015 Aug 12:S0145-2126(15)30356-8. doi: 10.1016/j.leukres.2015.08.003. Online ahead of print.

  PMID: 26364797 BACKGROUND

• 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 BACKGROUND

• Tefferi A, Cervantes F, Mesa R, Passamonti F, Verstovsek S, Vannucchi AM, Gotlib J, Dupriez B, Pardanani A, Harrison C, Hoffman R, Gisslinger H, Kroger N, Thiele J, Barbui T, Barosi G. Revised response criteria for myelofibrosis: International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European LeukemiaNet (ELN) consensus report. Blood. 2013 Aug 22;122(8):1395-8. doi: 10.1182/blood-2013-03-488098. Epub 2013 Jul 9.

  PMID: 23838352 BACKGROUND

MeSH Terms

Conditions

Primary Myelofibrosis; Anemia

Condition Hierarchy (Ancestors)

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

Study Officials

• Sandra Malak, MD

  Hôpital René Huguenin - Institut Curie - St Cloud - France

  PRINCIPAL INVESTIGATOR

• Lydia Roy, MD

  Hôpital Henri Mondor - Créteil - France

  STUDY DIRECTOR

• Pascale Cony-Makhoul, MD

  CH Annecy Genevois - Pringy - France

  STUDY DIRECTOR

• Mathieu Wemeau, MD

  CH Arras

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 28, 2017
• First Posted: July 6, 2017
• Study Start: May 1, 2016
• Primary Completion: December 31, 2016
• Study Completion: December 31, 2016
• Last Updated: July 20, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share