TY - JOUR
T1 - Clinical end points for drug treatment trials in BCR-ABL1-negative classic myeloproliferative neoplasms
T2 - Consensus statements from European LeukemiaNET (ELN) and Internation Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT)
AU - Barosi, G.
AU - Tefferi, A.
AU - Besses, C.
AU - Birgegard, G.
AU - Cervantes, F.
AU - Finazzi, G.
AU - Gisslinger, H.
AU - Griesshammer, M.
AU - Harrison, C.
AU - Hehlmann, R.
AU - Hermouet, S.
AU - Kiladjian, J. J.
AU - Kröger, N.
AU - Mesa, R.
AU - Mc Mullin, M. F.
AU - Pardanani, A.
AU - Passamonti, F.
AU - Samuelsson, J.
AU - Vannucchi, A. M.
AU - Reiter, A.
AU - Silver, R. T.
AU - Verstovsek, S.
AU - Tognoni, G.
AU - Barbui, T.
N1 - Publisher Copyright:
© 2015 Macmillan Publishers Limited.
PY - 2015/1/10
Y1 - 2015/1/10
N2 - 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.
AB - 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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U2 - 10.1038/leu.2014.250
DO - 10.1038/leu.2014.250
M3 - Review article
C2 - 25151955
AN - SCOPUS:84920646510
SN - 0887-6924
VL - 29
SP - 20
EP - 26
JO - Leukemia
JF - Leukemia
IS - 1
ER -