Phase 1 study of selinexor plus carfilzomib and dexamethasone for the treatment of relapsed/refractory multiple myeloma.
Aged
Antineoplastic Combined Chemotherapy Protocols
/ adverse effects
Cytogenetic Analysis
Dexamethasone
/ administration & dosage
Drug Resistance, Neoplasm
Female
Humans
Hydrazines
/ administration & dosage
Male
Middle Aged
Multiple Myeloma
/ drug therapy
Neoplasm Staging
Oligopeptides
/ administration & dosage
Prognosis
Recurrence
Retreatment
Treatment Outcome
Triazoles
/ administration & dosage
carfilzomib
dexamethasone
relapsed/refractory multiple myeloma
selinexor
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
26
11
2018
accepted:
22
03
2019
pubmed:
28
5
2019
medline:
4
6
2020
entrez:
25
5
2019
Statut:
ppublish
Résumé
Selinexor, an oral Selective Inhibitor of Nuclear Export, targets Exportin 1 (XPO1, also termed CRM1). Non-clinical studies support combining selinexor with proteasome inhibitors (PIs) and corticosteroids to overcome resistance in relapsed/refractory multiple myeloma (RRMM). We conducted a phase I dose-escalation trial of twice-weekly selinexor in combination with carfilzomib and dexamethasone (SKd) to determine maximum tolerated dose in patients with RRMM (N = 21), with an expansion cohort to assess activity in carfilzomib-refractory disease and identify a recommended phase II dose (RP2D). During dose escalation, there was one dose-limiting toxicity (cardiac failure). The RP2D of twice-weekly SKd was selinexor 60 mg, carfilzomib 20/27 mg/m
Identifiants
pubmed: 31124580
doi: 10.1111/bjh.15969
pmc: PMC6772147
doi:
Substances chimiques
Hydrazines
0
Oligopeptides
0
Triazoles
0
selinexor
31TZ62FO8F
carfilzomib
72X6E3J5AR
Dexamethasone
7S5I7G3JQL
Banques de données
ClinicalTrials.gov
['NCT02199665']
Types de publication
Clinical Trial, Phase I
Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
549-560Informations de copyright
© 2019 British Society for Haematology and John Wiley & Sons Ltd.
Références
Cell Rep. 2012 Aug 30;2(2):207-15
pubmed: 22902403
Haematologica. 2009 Feb;94(2):270-5
pubmed: 19144659
Haematologica. 2015 May;100(5):670-6
pubmed: 25710456
Lancet Oncol. 2016 Jan;17(1):27-38
pubmed: 26671818
J Clin Oncol. 2015 Mar 1;33(7):732-9
pubmed: 25225420
Leukemia. 2018 Feb;32(2):252-262
pubmed: 29257139
Leukemia. 2014 Jan;28(1):155-65
pubmed: 23588715
J Clin Oncol. 2018 Mar 20;36(9):859-866
pubmed: 29381435
Blood. 2013 Mar 14;121(11):1961-7
pubmed: 23243282
Blood. 2017 Aug 31;130(9):1132-1143
pubmed: 28630120
Clin Cancer Res. 2017 Aug 1;23(15):4301-4311
pubmed: 28314790
Biomark Res. 2013 Mar 01;1(1):13
pubmed: 24252210
Onco Targets Ther. 2016 Aug 05;9:4843-58
pubmed: 27540299
Exp Hematol Oncol. 2015 Mar 01;4:7
pubmed: 25745591
Blood. 2008 Mar 1;111(5):2516-20
pubmed: 17975015
Oncotarget. 2016 Nov 29;7(48):78896-78909
pubmed: 27806331
Blood. 2018 Feb 22;131(8):855-863
pubmed: 29203585
Blood. 2012 Oct 4;120(14):2817-25
pubmed: 22833546
Cancer Res. 2012 Feb 1;72(3):757-68
pubmed: 22147262
Mol Cancer Res. 2008 Aug;6(8):1356-64
pubmed: 18708367
Oncotarget. 2016 Nov 29;7(48):78883-78895
pubmed: 27713151
Leukemia. 2014 Jul;28(7):1529-36
pubmed: 24429497
Blood. 2014 Mar 20;123(12):1826-32
pubmed: 24421329
Blood. 2015 Nov 12;126(20):2284-90
pubmed: 26384354
Mol Cancer Ther. 2016 Jan;15(1):60-71
pubmed: 26637366
JAMA Oncol. 2018 Mar 08;4(3):e174519
pubmed: 29285538
Lancet Oncol. 2017 Oct;18(10):1327-1337
pubmed: 28843768
Blood. 2018 Dec 13;132(24):2546-2554
pubmed: 30352784
Blood. 2015 May 14;125(20):3085-99
pubmed: 25838342
Clin Lymphoma Myeloma Leuk. 2018 May;18(5):335-345
pubmed: 29610030
Blood. 2016 Jul 28;128(4):497-503
pubmed: 27226434
Int J Biochem Mol Biol. 2012;3(2):137-51
pubmed: 22773955
Blood. 2016 Jun 30;127(26):3360-8
pubmed: 27207788
J Natl Compr Canc Netw. 2018 Jan;16(1):11-20
pubmed: 29295877
Cardiooncology. 2017 Jun 01;3:4
pubmed: 32154000
Haematologica. 2016 Apr;101(4):396-406
pubmed: 27033237
Leukemia. 2006 Sep;20(9):1467-73
pubmed: 16855634
Blood. 2011 May 5;117(18):4691-5
pubmed: 21292775
Lancet Oncol. 2013 Oct;14(11):1055-1066
pubmed: 24007748
J Hematol Oncol. 2014 Dec 05;7:85
pubmed: 25476752
Clin Cancer Res. 2015 Oct 15;21(20):4508-13
pubmed: 26324742
Leukemia. 2013 Dec;27(12):2357-65
pubmed: 23752175