Open AccessClinical 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)
Author(s) -
Giovanni Barosi,
Ayalew Tefferi,
Carlos Besses,
Gunnar Birgegård,
Francisco Cervantes,
Guido Finazzi,
Heinz Gisslinger,
Martin Grießhammer,
Claire Harrison,
Rüdiger Hehlmann,
Sylvie Hermouet,
JeanJacques Kiladjian,
Nicolaus Kröger,
Ruben A. Mesa,
Mary Frances Mc Mullin,
Animesh Pardanani,
Francesco Passamonti,
Jan Samuelsson,
Alessandro M. Vannucchi,
Andreas Reiter,
Richard T. Silver,
Srđan Verstovšek,
Gianni Togi,
Tiziano Barbui
Publication year - 2014
Publication title -
leukemia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.539
H-Index - 192
eISSN - 1476-5551
pISSN - 0887-6924
DOI - 10.1038/leu.2014.250
Subject(s) - medicine , essential thrombocythemia , myelofibrosis , polycythemia vera , clinical trial , clinical endpoint , oncology , clinical research , population , ruxolitinib , randomized controlled trial , bone marrow , environmental health
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.