Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT).
Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms: consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT).
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DOI：
10.1038/leu.2014.250
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发表时间：
2015-01
期刊：
影响因子：
11.4
通讯作者：
Barbui T
中科院分区：
文献类型：
--
作者：
Barosi G;Tefferi A;Besses C;Birgegard G;Cervantes F;Finazzi G;Gisslinger H;Griesshammer M;Harrison C;Hehlmann R;Hermouet S;Kiladjian JJ;Kröger N;Mesa R;Mc Mullin MF;Pardanani A;Passamonti F;Samuelsson J;Vannucchi AM;Reiter A;Silver RT;Verstovsek S;Tognoni G;Barbui T
在经典的BCR-ABL 1阴性骨髓增生性肿瘤（MPN）中发现体细胞突变，主要是JAK 2 V617 F和CALR，引起了人们对分子靶向治疗开发的兴趣，其准确评估需要标准化框架。一个由欧洲白血病网络（ELN）和国际MPN研究和治疗工作组（IWG-MRT）成员组成的工作组，就试验设计、患者选择和相关终点定义提出了基于共识的建议。因此，应选择能够获得药物长期效应的反应作为旨在开发MPN新药的II期试验的终点。至事件发生时间，如总生存期或无进展生存期或两者，作为共同主要终点，应在III期研究中衡量疗效。应在随机研究中对预防早期疾病骨髓纤维化患者疾病进展的新药进行测试，并将事件发生时间（如无进展或无事件生存期）作为主要终点。旨在预防真性红细胞增多症和原发性血小板增多症血管事件的III期试验应基于新的预后因素（包括JAK 2突变）选择目标人群。总之，我们推荐了一种MPN临床试验的格式，以促进学术研究者、监管机构和制药公司之间的沟通。
The discovery of somatic mutations, primarily JAK2V617F and CALR, in classic BCR-ABL1-negative myeloproliferative neoplasms (MPNs) has generated interest in the development of molecularly targeted therapies, whose accurate assessment requires a standardized framework. A working group, comprised of members from European LeukemiaNet (ELN) and International Working Group for MPN Research and Treatment (IWG-MRT), prepared consensus-based recommendations regarding trial design, patient selection and definition of relevant end points. Accordingly, a response able to capture the long-term effect of the drug should be selected as the end point of phase II trials aimed at developing new drugs for MPNs. A time-to-event, such as overall survival, or progression-free survival or both, as co-primary end points, should measure efficacy in phase III studies. New drugs should be tested for preventing disease progression in myelofibrosis patients with early disease in randomized studies, and a time to event, such as progression-free or event-free survival should be the primary end point. Phase III trials aimed at preventing vascular events in polycythemia vera and essential thrombocythemia should be based on a selection of the target population based on new prognostic factors, including JAK2 mutation. In conclusion, we recommended a format for clinical trials in MPNs that facilitates communication between academic investigators, regulatory agencies and drug companies.
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影响因子：
20.3
作者：
Guglielmelli, Paola;Barosi, Giovanni;Vannucchi, Alessandro M.
通讯作者：
Vannucchi, Alessandro M.
预纤维化的骨髓纤维化沿临床和生物连续体排列的证据，具有原发性骨髓纤维化。
影响因子：
3.7
作者：
Barosi G;Rosti V;Bonetti E;Campanelli R;Carolei A;Catarsi P;Isgrò AM;Lupo L;Massa M;Poletto V;Viarengo G;Villani L;Magrini U
通讯作者：
Magrini U
影响因子：
45.3
作者：
Emanuel, Robyn M.;Dueck, Amylou C.;Mesa, Ruben A.
通讯作者：
Mesa, Ruben A.
影响因子：
5.7
作者：
Fiskus, Warren;Verstovsek, Srdan;Bhalla, Kapil N.
通讯作者：
Bhalla, Kapil N.
影响因子：
20.3
作者：
Kiladjian, Jean-Jacques;Cassinat, Bruno;Fenaux, Pierre
通讯作者：
Fenaux, Pierre