Ruxolitinib in Myelofibrosis Patients in Lombardy, Italy

Myelofibrosis Clinical Trial

Official title:

Observational, Retrospective and Prospective Study on the Use of Ruxolitinib in Myelofibrosis Patients in Lombardy, Italy

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03959371
• Other study ID #: RUXOREL-MF
• Status: Recruiting
• Start date: April 11, 2017
• Est. completion date: December 31, 2021

Study information

• Verified date: May 2019
• Source: Ospedale di Circolo - Fondazione Macchi
• Contact: Margherita Maffioli, MD
• Phone: +39-0332-278281
• Email: margherita.maffioli[@]asst-settelaghi.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The RUXOREL-MF observational study includes patients with primary and post-essential thrombocythemia/post-polycythemia vera myelofibrosis (MF) being treated with the oral JAK1-/JAK2-inhibitor ruxolitinib in a "real world" setting. Patients are treated according to current indications in Italy (i.e., primary and secondary MF patients with intermediate-1, intermediate-2, and high risk IPSS (International Prognostic Scoring System) scores and symptomatic splenomegaly and/or systemic symptoms). Patients are treated at facilities pertaining to the regional Hematology Network of Lombardy (Rete Ematologica Lombarda) in Italy. Efficacy data, data related to infectious and vascular events, data related to second primary malignancies, data regarding disease progression/transformation, and molecular information in relationship to ruxolitinib treatment will be collected and analyzed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 620
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age >= 18 years

• Diagnosis of primary myelofibrosis diagnosis according to the WHO 2016 classification or post-essential thrombocythemia/post-polycythemia vera myelofibrosis according to the IWG-MRT 2008 classification

• Patients with an intermediate-1, intermediate-2, or high risk score according to the IPSS (International Prognostic Scoring System)

• Patients treated with ruxolitinib in accordance with current indications in Italy

• Patients eligible or ineligible to hematopoietic stem cell transplant or who have already undergone a hematopoietic stem cell transplant

Exclusion Criteria:

• Diagnoses other than primary myelofibrosis or post-essential thrombocythemia/post-polycythemia vera myelofibrosis

• Patients treated with ruxolitinib having a platelet count at treatment initiation <50 x10^9/L

• Patients treated with ruxolitinib for conditions other than primary myelofibrosis or post-essential thrombocythemia/post-polycythemia vera myelofibrosis

Related Conditions & MeSH terms

• Myelofibrosis
• Primary Myelofibrosis

Intervention

Drug:
• Ruxolitinib
Observational study including patients with myelofibrosis being treated with ruxolitinib in a "real world" setting. Patients are treated according to current indications.

Locations

Country	Name	City	State
Italy	ASST Papa Giovanni XXIII	Bergamo
Italy	U.O. Ematologia, ASST Spedali Civili	Brescia
Italy	U.S.D. Trapianti di Midollo Osseo, ASST Spedali Civili	Brescia
Italy	U.O.C. di Ematologia Clinica, ASST Lecco	Lecco
Italy	U.O. Ematologia, ASST Fatebenefratelli-Sacco	Milan
Italy	U.O. Ematologia, Fondazione IRCCS Istituto Nazionale Tumori	Milan
Italy	U.O. Ematologia, Grande Ospedale Metropolitano Niguarda	Milan
Italy	U.O. Ematologia, Humanicas Cancer Center	Milan
Italy	U.O. Ematologia, Ospedale San Raffaele	Milan
Italy	U.O. Oncoematologia, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico	Milan
Italy	Clinica Ematologica, Ospedale San Gerardo	Monza
Italy	Ospedale di Circolo, ASST Sette Laghi	Varese

Sponsors (1)

Lead Sponsor	Collaborator
Margherita Maffioli

Country where clinical trial is conducted

Italy, 

References & Publications (24)

Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, Bloomfield CD, Cazzola M, Vardiman JW. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016 May 19;127(20):2391-405. doi: 10.1182/blood-2016-03-643544. Epub 2016 Apr 11. Review. — View Citation

Barosi G, Mesa RA, Thiele J, Cervantes F, Campbell PJ, Verstovsek S, Dupriez B, Levine RL, Passamonti F, Gotlib J, Reilly JT, Vannucchi AM, Hanson CA, Solberg LA, Orazi A, Tefferi A; International Working Group for Myelofibrosis Research and Treatment (IWG-MRT). Proposed criteria for the diagnosis of post-polycythemia vera and post-essential thrombocythemia myelofibrosis: a consensus statement from the International Working Group for Myelofibrosis Research and Treatment. Leukemia. 2008 Feb;22(2):437-8. Epub 2007 Aug 30. — View Citation

Caramazza D, Begna KH, Gangat N, Vaidya R, Siragusa S, Van Dyke DL, Hanson C, Pardanani A, Tefferi A. Refined cytogenetic-risk categorization for overall and leukemia-free survival in primary myelofibrosis: a single center study of 433 patients. Leukemia. 2011 Jan;25(1):82-8. doi: 10.1038/leu.2010.234. Epub 2010 Oct 14. — View Citation

Cervantes F, Dupriez B, Pereira A, Passamonti F, Reilly JT, Morra E, Vannucchi AM, Mesa RA, Demory JL, Barosi G, Rumi E, Tefferi A. New prognostic scoring system for primary myelofibrosis based on a study of the International Working Group for Myelofibrosis Research and Treatment. Blood. 2009 Mar 26;113(13):2895-901. doi: 10.1182/blood-2008-07-170449. Epub 2008 Nov 6. — View Citation

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. Erratum in: Blood. 2016 Dec 22;128(25):3013. — View Citation

Gangat N, Caramazza D, Vaidya R, George G, Begna K, Schwager S, Van Dyke D, Hanson C, Wu W, Pardanani A, Cervantes F, Passamonti F, Tefferi A. DIPSS plus: a refined Dynamic International Prognostic Scoring System for primary myelofibrosis that incorporates prognostic information from karyotype, platelet count, and transfusion status. J Clin Oncol. 2011 Feb 1;29(4):392-7. doi: 10.1200/JCO.2010.32.2446. Epub 2010 Dec 13. — View Citation

Guglielmelli P, Biamonte F, Rotunno G, Artusi V, Artuso L, Bernardis I, Tenedini E, Pieri L, Paoli C, Mannarelli C, Fjerza R, Rumi E, Stalbovskaya V, Squires M, Cazzola M, Manfredini R, Harrison C, Tagliafico E, Vannucchi AM; COMFORT-II Investigators; Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative (AGIMM) Investigators. Impact of mutational status on outcomes in myelofibrosis patients treated with ruxolitinib in the COMFORT-II study. Blood. 2014 Apr 3;123(14):2157-60. doi: 10.1182/blood-2013-11-536557. Epub 2014 Jan 23. — View Citation

Guglielmelli P, Lasho TL, Rotunno G, Mudireddy M, Mannarelli C, Nicolosi M, Pacilli A, Pardanani A, Rumi E, Rosti V, Hanson CA, Mannelli F, Ketterling RP, Gangat N, Rambaldi A, Passamonti F, Barosi G, Barbui T, Cazzola M, Vannucchi AM, Tefferi A. MIPSS70: Mutation-Enhanced International Prognostic Score System for Transplantation-Age Patients With Primary Myelofibrosis. J Clin Oncol. 2018 Feb 1;36(4):310-318. doi: 10.1200/JCO.2017.76.4886. Epub 2017 Dec 9. — View Citation

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. — View Citation

Harrison CN, Vannucchi AM, Kiladjian JJ, Al-Ali HK, Gisslinger H, Knoops L, Cervantes F, Jones MM, Sun K, McQuitty M, Stalbovskaya V, Gopalakrishna P, Barbui T. Long-term findings from COMFORT-II, a phase 3 study of ruxolitinib vs best available therapy for myelofibrosis. Leukemia. 2016 Aug;30(8):1701-7. doi: 10.1038/leu.2016.148. Epub 2016 May 23. Erratum in: Leukemia. 2017 Mar;31(3):775. — View Citation

Heine A, Brossart P, Wolf D. Ruxolitinib is a potent immunosuppressive compound: is it time for anti-infective prophylaxis? Blood. 2013 Nov 28;122(23):3843-4. doi: 10.1182/blood-2013-10-531103. — View Citation

Kröger NM, Deeg JH, Olavarria E, Niederwieser D, Bacigalupo A, Barbui T, Rambaldi A, Mesa R, Tefferi A, Griesshammer M, Gupta V, Harrison C, Alchalby H, Vannucchi AM, Cervantes F, Robin M, Ditschkowski M, Fauble V, McLornan D, Ballen K, Popat UR, Passamonti F, Rondelli D, Barosi G. Indication and management of allogeneic stem cell transplantation in primary myelofibrosis: a consensus process by an EBMT/ELN international working group. Leukemia. 2015 Nov;29(11):2126-33. doi: 10.1038/leu.2015.233. Epub 2015 Aug 21. Review. — View Citation

Newberry KJ, Patel K, Masarova L, Luthra R, Manshouri T, Jabbour E, Bose P, Daver N, Cortes J, Kantarjian H, Verstovsek S. Clonal evolution and outcomes in myelofibrosis after ruxolitinib discontinuation. Blood. 2017 Aug 31;130(9):1125-1131. doi: 10.1182/blood-2017-05-783225. Epub 2017 Jul 3. — View Citation

Passamonti F, Cervantes F, Vannucchi AM, Morra E, Rumi E, Pereira A, Guglielmelli P, Pungolino E, Caramella M, Maffioli M, Pascutto C, Lazzarino M, Cazzola M, Tefferi A. A dynamic prognostic model to predict survival in primary myelofibrosis: a study by the IWG-MRT (International Working Group for Myeloproliferative Neoplasms Research and Treatment). Blood. 2010 Mar 4;115(9):1703-8. doi: 10.1182/blood-2009-09-245837. Epub 2009 Dec 14. — View Citation

Passamonti F, Giorgino T, Mora B, Guglielmelli P, Rumi E, Maffioli M, Rambaldi A, Caramella M, Komrokji R, Gotlib J, Kiladjian JJ, Cervantes F, Devos T, Palandri F, De Stefano V, Ruggeri M, Silver RT, Benevolo G, Albano F, Caramazza D, Merli M, Pietra D, Casalone R, Rotunno G, Barbui T, Cazzola M, Vannucchi AM. A clinical-molecular prognostic model to predict survival in patients with post polycythemia vera and post essential thrombocythemia myelofibrosis. Leukemia. 2017 Dec;31(12):2726-2731. doi: 10.1038/leu.2017.169. Epub 2017 May 31. — View Citation

Passamonti F, Maffioli M. Update from the latest WHO classification of MPNs: a user's manual. Hematology Am Soc Hematol Educ Program. 2016 Dec 2;2016(1):534-542. Review. — View Citation

Passamonti F, Mora B, Giorgino T, Guglielmelli P, Cazzola M, Maffioli M, Rambaldi A, Caramella M, Komrokji R, Gotlib J, Kiladjian JJ, Cervantes F, Devos T, Palandri F, De Stefano V, Ruggeri M, Silver R, Benevolo G, Albano F, Caramazza D, Rumi E, Merli M, Pietra D, Casalone R, Barbui T, Pieri L, Vannucchi AM. Driver mutations' effect in secondary myelofibrosis: an international multicenter study based on 781 patients. Leukemia. 2017 Apr;31(4):970-973. doi: 10.1038/leu.2016.351. Epub 2016 Nov 25. — View Citation

Rotunno G, Pacilli A, Artusi V, Rumi E, Maffioli M, Delaini F, Brogi G, Fanelli T, Pancrazzi A, Pietra D, Bernardis I, Belotti C, Pieri L, Sant'Antonio E, Salmoiraghi S, Cilloni D, Rambaldi A, Passamonti F, Barbui T, Manfredini R, Cazzola M, Tagliafico E, Vannucchi AM, Guglielmelli P. Epidemiology and clinical relevance of mutations in postpolycythemia vera and postessential thrombocythemia myelofibrosis: A study on 359 patients of the AGIMM group. Am J Hematol. 2016 Jul;91(7):681-6. doi: 10.1002/ajh.24377. Epub 2016 May 11. — View Citation

Rumi E, Pietra D, Pascutto C, Guglielmelli P, Martínez-Trillos A, Casetti I, Colomer D, Pieri L, Pratcorona M, Rotunno G, Sant'Antonio E, Bellini M, Cavalloni C, Mannarelli C, Milanesi C, Boveri E, Ferretti V, Astori C, Rosti V, Cervantes F, Barosi G, Vannucchi AM, Cazzola M; Associazione Italiana per la Ricerca sul Cancro Gruppo Italiano Malattie Mieloproliferative Investigators. Clinical effect of driver mutations of JAK2, CALR, or MPL in primary myelofibrosis. Blood. 2014 Aug 14;124(7):1062-9. doi: 10.1182/blood-2014-05-578435. Epub 2014 Jul 1. — View Citation

Spiegel JY, McNamara C, Kennedy JA, Panzarella T, Arruda A, Stockley T, Sukhai M, Thomas M, Bartoszko J, Ho J, Siddiq N, Maze D, Schimmer A, Schuh A, Sibai H, Yee K, Claudio J, Devlin R, Minden MD, Kamel-Reid S, Gupta V. Impact of genomic alterations on outcomes in myelofibrosis patients undergoing JAK1/2 inhibitor therapy. Blood Adv. 2017 Sep 8;1(20):1729-1738. doi: 10.1182/bloodadvances.2017009530. eCollection 2017 Sep 12. — View Citation

Thiele J, Kvasnicka HM, Facchetti F, Franco V, van der Walt J, Orazi A. European consensus on grading bone marrow fibrosis and assessment of cellularity. Haematologica. 2005 Aug;90(8):1128-32. — View Citation

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. — View Citation

Vannucchi AM, Lasho TL, Guglielmelli P, Biamonte F, Pardanani A, Pereira A, Finke C, Score J, Gangat N, Mannarelli C, Ketterling RP, Rotunno G, Knudson RA, Susini MC, Laborde RR, Spolverini A, Pancrazzi A, Pieri L, Manfredini R, Tagliafico E, Zini R, Jones A, Zoi K, Reiter A, Duncombe A, Pietra D, Rumi E, Cervantes F, Barosi G, Cazzola M, Cross NC, Tefferi A. Mutations and prognosis in primary myelofibrosis. Leukemia. 2013 Sep;27(9):1861-9. doi: 10.1038/leu.2013.119. Epub 2013 Apr 26. — View Citation

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. — View Citation

* Note: There are 24 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of infectious events after ruxolitinib exposure in myelofibrosis patients		Through study completion, an average of 1 year
Primary	Rate of vascular events after ruxolitinib exposure in myelofibrosis patients		Through study completion, an average of 1 year
Secondary	Spleen response rate		At 3 and 6 months from ruxolitinib start
Secondary	Rate of primary secondary malignancies		Through study completion, an average of 1 year
Secondary	Acute myeloid leukemia transformation rate		Through study completion, an average of 1 year
Secondary	Rate of infectious events according to driver mutational status (i.e., mutations of JAK2, CALR, or MPL)	Association of rate of infectious events with driver mutational status	Through study completion, an average of 1 year
Secondary	Rate of vascular events according to driver mutational status (i.e., mutations of JAK2, CALR, or MPL)	Association of rate of vascular events with driver mutational status	Through study completion, an average of 1 year
Secondary	Spleen response rate according to driver mutational status (i.e., mutations of JAK2, CALR, or MPL)	Association of spleen response rate with driver mutational status	Through study completion, an average of 1 year
Secondary	Rate of primary secondary malignancies according to driver mutational status (i.e., mutations of JAK2, CALR, or MPL)	Association of rate of primary secondary malignancies with driver mutational status	Through study completion, an average of 1 year
Secondary	Acute myeloid leukemia transformation rate according to driver mutational status (i.e., mutations of JAK2, CALR, or MPL)	Association of acute myeloid leukemia transformation rate with driver mutational status	Through study completion, an average of 1 year
Secondary	Rate of infectious events according to the presence of additional mutations	Association of rate of infectious events with the presence of additional mutations	Through study completion, an average of 1 year
Secondary	Rate of vascular events according to the presence of additional mutations	Association of rate of vascular events with the presence of additional mutations	Through study completion, an average of 1 year
Secondary	Spleen response rate according to the presence of additional mutations	Association of spleen response rate with the presence of additional mutations	Through study completion, an average of 1 year
Secondary	Rate of primary secondary malignancies according to the presence of additional mutations	Association of rate of primary secondary malignancies with the presence of additional mutations	Through study completion, an average of 1 year
Secondary	Acute myeloid leukemia transformation rate according to the presence of additional mutations	Association of acute myeloid leukemia transformation rate with the presence of additional mutations	Through study completion, an average of 1 year
Secondary	Evaluation of overall survival after ruxolitinib start and, if applicable, discontinuation		Through study completion, an average of 1 year