PMID- 28622623
OWN - NLM
STAT- MEDLINE
DCOM- 20171031
LR  - 20210604
IS  - 1873-5835 (Electronic)
IS  - 0145-2126 (Print)
IS  - 0145-2126 (Linking)
VI  - 60
DP  - 2017 Sep
TI  - A phase 2 study of momelotinib, a potent JAK1 and JAK2 inhibitor, in patients 
      with polycythemia vera or essential thrombocythemia.
PG  - 11-17
LID - S0145-2126(17)30416-2 [pii]
LID - 10.1016/j.leukres.2017.05.002 [doi]
AB  - Momelotinib is a potent inhibitor of JAK1 and JAK2 that demonstrated efficacy in 
      patients with primary and secondary myelofibrosis. This phase 2, open-label, 
      randomized study evaluated the efficacy and safety of oral once-daily momelotinib 
      (100mg and 200mg) for the treatment of polycythemia vera (PV) and essential 
      thrombocythemia (ET). The primary endpoint for PV was overall response rate 
      (ORR), defined as the proportion of patients with hematocrit <45%, white blood 
      cell count <10x10(9)/L, platelet count </=400x10(9)/L, and resolution of palpable 
      splenomegaly, each lasting >/=4 weeks. The definition of ORR for ET excluded the 
      hematocrit component. A total of 39 patients (28 PV, 11 ET) were enrolled, with 
      28 patients receiving >/=12 weeks of treatment. The study was terminated due to 
      limited efficacy. Two patients (ORR 5.1%) met the primary efficacy endpoint (both 
      PV 200mg). Predose plasma levels of momelotinib were stable over time. A total of 
      31 (79.5%) patients experienced momelotinib-related adverse events (AEs), the 
      most frequent being headache (23.1%), dizziness (18.0%), somnolence (15.4%), 
      nausea (15.4%), and fatigue (15.4%). Three patients experienced serious AEs 
      (7.7%), with 1 considered related to momelotinib (dyspnea). Peripheral neuropathy 
      occurred in 7 (17.9%) patients (4 PV, 3 ET).
CI  - Copyright (c) 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.
FAU - Verstovsek, Srdan
AU  - Verstovsek S
AD  - The University of Texas, MD Anderson Cancer Center, Houston, TX, USA. Electronic 
      address: kjnewber@mdanderson.org.
FAU - Courby, Stephane
AU  - Courby S
AD  - Centre Hospitalier Universitaire de Grenoble, Grenoble, France.
FAU - Griesshammer, Martin
AU  - Griesshammer M
AD  - Johannes Wesling Klinikum Minden, University of Bochum, Germany.
FAU - Mesa, Ruben A
AU  - Mesa RA
AD  - Mayo Clinic, Scottsdale, AZ, USA.
FAU - Brachmann, Carrie Baker
AU  - Brachmann CB
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Kawashima, Jun
AU  - Kawashima J
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Maltzman, Julia D
AU  - Maltzman JD
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Shao, Lixin
AU  - Shao L
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Xin, Yan
AU  - Xin Y
AD  - Gilead Sciences, Inc., Foster City, CA, USA.
FAU - Huang, Daniel
AU  - Huang D
AD  - The Oncology Institute of Hope and Innovation, Santa Ana, CA, USA.
FAU - Bajel, Ashish
AU  - Bajel A
AD  - Department of Clinical Haematology and Bone Marrow Transplantation, Royal 
      Melbourne Hospital, Victoria, Australia.
LA  - eng
SI  - ClinicalTrials.gov/NCT01998828
GR  - P30 CA054174/CA/NCI NIH HHS/United States
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20170530
PL  - England
TA  - Leuk Res
JT  - Leukemia research
JID - 7706787
RN  - 0 (Benzamides)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 6O01GMS00P 
      (N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide)
RN  - EC 2.7.10.2 (JAK1 protein, human)
RN  - EC 2.7.10.2 (JAK2 protein, human)
RN  - EC 2.7.10.2 (Janus Kinase 1)
RN  - EC 2.7.10.2 (Janus Kinase 2)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Benzamides/adverse effects/*therapeutic use
MH  - Female
MH  - Humans
MH  - Janus Kinase 1/antagonists & inhibitors
MH  - Janus Kinase 2/antagonists & inhibitors
MH  - Male
MH  - Middle Aged
MH  - Polycythemia Vera/*drug therapy
MH  - Protein Kinase Inhibitors/adverse effects/*therapeutic use
MH  - Pyrimidines/adverse effects/*therapeutic use
MH  - Thrombocythemia, Essential/*drug therapy
MH  - Treatment Outcome
PMC - PMC8170698
MID - NIHMS1698100
OTO - NOTNLM
OT  - Essential thrombocythemia
OT  - Momelotinib
OT  - Phase 2 study
OT  - Polycythemia vera
EDAT- 2017/06/18 06:00
MHDA- 2017/11/01 06:00
PMCR- 2021/06/02
CRDT- 2017/06/17 06:00
PHST- 2017/01/19 00:00 [received]
PHST- 2017/05/04 00:00 [accepted]
PHST- 2017/06/18 06:00 [pubmed]
PHST- 2017/11/01 06:00 [medline]
PHST- 2017/06/17 06:00 [entrez]
PHST- 2021/06/02 00:00 [pmc-release]
AID - S0145-2126(17)30416-2 [pii]
AID - 10.1016/j.leukres.2017.05.002 [doi]
PST - ppublish
SO  - Leuk Res. 2017 Sep;60:11-17. doi: 10.1016/j.leukres.2017.05.002. Epub 2017 May 
      30.