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)

G Barosi, A Tefferi, C Besses, G Birgegard, F Cervantes, G Finazzi, H Gisslinger, M Griesshammer, C Harrison, R Hehlmann, S Hermouet, J-J Kiladjian, N Kröger, R Mesa, M F McMullin, A Pardanani, F Passamonti, J Samuelsson, A M Vannucchi, A ReiterR T Silver, S Verstovsek, G Tognoni, T Barbui

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)20-26
Number of pages7
JournalLeukemia
Volume29
Early online date19 Sep 2014
DOIs
Publication statusPublished - 2015

Keywords

  • Consensus
  • Endpoint Determination
  • Fusion Proteins, bcr-abl
  • Humans
  • Myeloproliferative Disorders
  • Prognosis

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