Ignite Creation Date:
2025-12-24 @ 7:46 PM
Ignite Modification Date:
2026-01-01 @ 11:19 AM
Study NCT ID:
NCT03208803
Status:
COMPLETED
Last Update Posted:
2022-07-20
First Post:
2017-06-28
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Combination of JAK2 Inhibitor and Erythropoiesis-stimulating Agent in Myelofibrosis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D055728', 'term': 'Primary Myelofibrosis'}, {'id': 'D000740', 'term': 'Anemia'}], 'ancestors': [{'id': 'D009196', 'term': 'Myeloproliferative Disorders'}, {'id': 'D001855', 'term': 'Bone Marrow Diseases'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}]}}, 'protocolSection': {'designModule': {'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'OTHER', 'observationalModel': 'CASE_ONLY'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 65}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2016-05', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2022-07', 'completionDateStruct': {'date': '2016-12-31', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2022-07-19', 'studyFirstSubmitDate': '2017-06-28', 'studyFirstSubmitQcDate': '2017-07-03', 'lastUpdatePostDateStruct': {'date': '2022-07-20', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2017-07-06', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-12-31', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Effect on anemia of the combination Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent', 'timeFrame': '6 months', 'description': 'Response rate assessed with 2006 International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Network (ELN) criteria'}], 'secondaryOutcomes': [{'measure': 'Patterns of the combination Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent', 'timeFrame': '6 months', 'description': 'Modalities of the combination (drugs of interest begun at the same or at different dates, order of the drug combination if started at different dates, duration of combination, doses of each drug)'}, {'measure': 'Patients and Myelofibrosis characteristics', 'timeFrame': 'at inclusion', 'description': 'Demographic characteristics of included patients, Characteristics of diseases (date of diagnosis, primary or secondary myelofibrosis, prognostic scores, level of hemoglobin, transfusion dependency, splenomegaly, mutations, delay between myelofibrosis diagnosis and Jak2 inhibitor treatment)'}, {'measure': 'Response rate of the combination treatment on constitutional symptoms of myelofibrosis', 'timeFrame': '3 years'}, {'measure': 'Response rate of the combination treatment on splenomegaly', 'timeFrame': '3 years', 'description': 'Splenomegaly size assessment'}, {'measure': 'Efficacy of the combination treatment on bone marrow fibrosis', 'timeFrame': '3 years', 'description': 'Assessment of bone marrow fibrosis change if bone marrow biopsy has been done'}, {'measure': 'Efficacy of the combination treatment on Janus Kinase 2 allelic burden change', 'timeFrame': '3 years', 'description': 'Assessment of Janus Kinase 2 allelic burden change if molecular evaluation has been done in blood'}, {'measure': 'Adverse Events on combination treatment', 'timeFrame': '3 years'}, {'measure': 'Overall survival on combination treatment', 'timeFrame': '3 years'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Myelofibrosis', 'Erythropoiesis-stimulating Agents', 'Janus Kinase 2 inhibitors', 'Ruxolitinib'], 'conditions': ['Myelofibrosis; Anemia']}, 'referencesModule': {'references': [{'pmid': '25232060', 'type': 'BACKGROUND', 'citation': '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': '15793561', 'type': 'BACKGROUND', 'citation': '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': '25616577', 'type': 'BACKGROUND', 'citation': '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': '24174625', 'type': 'BACKGROUND', '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.'}, {'pmid': '26364797', 'type': 'BACKGROUND', 'citation': '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': '26380150', 'type': 'BACKGROUND', 'citation': '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': '23838352', 'type': 'BACKGROUND', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nDespite 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.\n\nRuxo-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.', 'detailedDescription': 'Myeloproliferative Neoplasms are chronic diseases; they encompass Polycythemia Vera, Essential Thrombocythemia, and Primary Myelofibrosis with shared mutations that constitutively activate the physiologic signal-transduction pathways responsible for hematopoiesis. Myelofibroses may arise either as primary or antecedent to Polycythemia Vera and Essential Thrombocythemia. Myelofibrosis is the least common and the most aggressive of these diseases leading to death in 5 to 7 years due to bone marrow failure, massive splenomegaly related to extra medullary hematopoiesis, constitutional symptoms and cachexia.\n\nUntil recently, treatment of Myelofibrosis consisted of supportive care only, especially transfusions.\n\nSince 2005 driver mutations have been identified in more than 90% of patients with myeloproliferative neoplasms, providing substantial insight into their pathogenesis and leading to the development of JAK inhibitor drugs. Ruxolitinib, the first one available, has shown activity whatever the presence of Janus Kinase 2 mutation, in reducing splenomegaly, improving cytopenias, alleviating constitutional symptoms and finally improving survival (COMFORT I and II studies). In France, access to ruxolitinib has been possible since April 2011, before wider availability in November 2012.\n\nAnemia is a frequent issue in Myelofibrosis, which may be managed by the use of Erythropoiesis-stimulating Agent, leading to a 40-50% response rate in small studies.\n\nConsistent with its Janus Kinase 2 signalling inhibition, ruxolitinib therapy has been shown to be detrimental on the hemoglobin level, increasing the depth of anemia or transfusion need, especially during the first 12-24 weeks of treatment in the COMFORT studies.\n\nDespite 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.\n\nRuxo-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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': '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', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* patients with primary myelofibrosis or post-polycythemia myelofibrosis or post-essential thrombocythemia myelofibrosis\n* previously started with a combination of Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent, whatever the date during the course of their disease\n\nExclusion Criteria:\n\n\\- patients who denied participating to this observational study'}, 'identificationModule': {'nctId': 'NCT03208803', 'acronym': 'Ruxo-EPO', 'briefTitle': 'Combination of JAK2 Inhibitor and Erythropoiesis-stimulating Agent in Myelofibrosis', 'organization': {'class': 'OTHER', 'fullName': 'Centre Hospitalier Annecy Genevois'}, 'officialTitle': 'Patients With Myelofibrosis Treated With Combination of Janus Kinase 2 Inhibitor and Erythropoiesis-stimulating Agent. A French Observational Study.', 'orgStudyIdInfo': {'id': '15-10_Ruxo-EPO'}}, 'contactsLocationsModule': {'overallOfficials': [{'name': 'Sandra Malak, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Hôpital René Huguenin - Institut Curie - St Cloud - France'}, {'name': 'Lydia Roy, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Hôpital Henri Mondor - Créteil - France'}, {'name': 'Pascale Cony-Makhoul, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'CH Annecy Genevois - Pringy - France'}, {'name': 'Mathieu Wemeau, MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'CH Arras'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Centre Hospitalier Annecy Genevois', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}