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)

TY - JOUR

T1 - 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)

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

PY - 2014/8/25

Y1 - 2014/8/25

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.Leukemia advance online publication, 19 September 2014; doi:10.1038/leu.2014.250.

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.Leukemia advance online publication, 19 September 2014; doi:10.1038/leu.2014.250.

U2 - 10.1038/leu.2014.250

DO - 10.1038/leu.2014.250

M3 - SCORING: Journal article

C2 - 25151955

JO - LEUKEMIA

JF - LEUKEMIA

SN - 0887-6924

ER -