دورية أكاديمية
Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study
| العنوان: | Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study |
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| المؤلفون: | Lortholary, Olivier, Chandesris, Marie, Olivia, Livideanu, Cristina, Bulai, Paul, Carle F, Guillet, Gérard, Jassem, Ewa, Niedoszytko, Marek, Barete, Stéphane, Verstovsek, Srdan, Grattan, Clive, Damaj, Gandhi, Canioni, Danielle, Fraitag, Sylvie, Lhermitte, Ludovic, Lavialle, Sophie, Georgin, Frenzel, Laurent, Afrin, Lawrence, B, Hanssens, Katia, Agopian, Julie, Gaillard, Raphaël, Kinet, Jean-Pierre, Auclair, Christian, Mansfield, Colin, Moussy, Alain, Dubreuil, Patrice, Hermine, Olivier |
| المساهمون: | Centre d'infectiologie Necker-Pasteur CHU Necker, Institut Pasteur Paris (IP)-Hôpital Necker - Enfants Malades AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de référence des mastocytoses (CEREMAST), Hôpital Necker - Enfants Malades AP-HP, Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre hospitalier universitaire de Poitiers = Poitiers University Hospital (CHU de Poitiers La Milétrie ), University of Gdańsk (UG), Université Pierre et Marie Curie - Paris 6 (UPMC), MD Anderson Cancer Center Houston, The University of Texas Health Science Center at Houston (UTHealth), Norfolk & Norwich University Hospital, Norfolk & Norwich University Hospital, Colney Lane, Institut d'Hématologie de Basse-Normandie (IHBN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse Caen (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER, Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon AP-HP, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Minnesota Twin Cities (UMN), University of Minnesota System (UMN), Histopathologie humaine et Modèles animaux, Institut Pasteur Paris (IP), Harvard Medical School Boston (HMS), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS), AB Science, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes (IPC), Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), AB Science (Paris, France). |
| المصدر: | ISSN: 0140-6736. |
| بيانات النشر: | HAL CCSD Elsevier |
| سنة النشر: | 2017 |
| المجموعة: | Aix-Marseille Université: HAL |
| مصطلحات موضوعية: | MESH: Adult, MESH: Aged, 80 and over, MESH: Asthenia, MESH: Diarrhea, MESH: Double-Blind Method, MESH: Exanthema, MESH: Female, MESH: Humans, MESH: Male, MESH: Mastocytosis, Systemic, MESH: Middle Aged, MESH: Protein Kinase Inhibitors, MESH: Severity of Illness Index, MESH: Thiazoles, MESH: Treatment Outcome, MESH: Urticaria, MESH: Young Adult, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer |
| الوصف: | International audience ; BACKGROUND:Indolent systemic mastocytosis, including the subvariant of smouldering systemic mastocytosis, is a lifelong condition associated with reduced quality of life. Masitinib inhibits KIT and LYN kinases that are involved in indolent systemic mastocytosis pathogenesis. We aimed to assess safety and efficacy of masitinib versus placebo in severely symptomatic patients who were unresponsive to optimal symptomatic treatments.METHODS:In this randomised, double-blind, placebo-controlled, phase 3 study, we enrolled adults (aged 18-75 years) with indolent or smouldering systemic mastocytosis, according to WHO classification or documented mastocytosis based on histological criteria, at 50 centres in 15 countries. We excluded patients with cutaneous or non-severe systemic mastocytosis after a protocol amendment. Patients were centrally randomised (1:1) to receive either oral masitinib (6 mg/kg per day over 24 weeks with possible extension) or matched placebo with minimisation according to severe symptoms. The primary endpoint was cumulative response (≥75% improvement from baseline within weeks 8-24) in at least one severe baseline symptom from the following: pruritus score of 9 or more, eight or more flushes per week, Hamilton Rating Scale for Depression of 19 or more, or Fatigue Impact Scale of 75 or more. We assessed treatment effect using repeated measures methodology for rare diseases via the generalised estimating equation model in a modified intention-to-treat population, including all participants assigned to treatment minus those who withdrew due to a non-treatment-related cause. We assessed safety in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00814073.FINDINGS:Between Feb 19, 2009, and July 15, 2015, 135 patients were randomly assigned to masitinib (n=71) or placebo (n=64). By 24 weeks, masitinib was associated with a cumulative response of 18·7% in the primary endpoint (122·6 responses of 656·5 possible ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/28069279; hal-01787376; https://hal.science/hal-01787376Test; https://hal.science/hal-01787376/documentTest; https://hal.science/hal-01787376/file/Masitinib%20for%20treatment%20of%20severely%20symptomatic%20indolent%20systemic%20mastocytosis%20a%20randomised,%20placebo%20controlled%20phase%203%20study.pdfTest; PUBMED: 28069279 |
| DOI: | 10.1016/S0140-6736(16)31403-9 |
| الإتاحة: | https://doi.org/10.1016/S0140-6736Test(16)31403-9 https://hal.science/hal-01787376Test https://hal.science/hal-01787376/documentTest https://hal.science/hal-01787376/file/Masitinib%20for%20treatment%20of%20severely%20symptomatic%20indolent%20systemic%20mastocytosis%20a%20randomised,%20placebo%20controlled%20phase%203%20study.pdfTest |
| حقوق: | info:eu-repo/semantics/OpenAccess |
| رقم الانضمام: | edsbas.AB002063 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/S0140-6736(16)31403-9 |
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