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Phase I study of selinexor in combination with dexamethasone, ifosfamide, carboplatin, etoposide chemotherapy in patients with relapsed or refractory peripheral T-cell or natural-killer/T-cell lymphoma

Authors :
Tiffany Tang
Peter Martin
Nagavalli Somasundaram
Cindy Lim
Miriam Tao
Eileen Poon
Maica JD. Yunon
Shu Q. Toh
Sean X Yan
Mohamad Farid
Jason Y. Chan
Soon T. Lim
Source :
Haematologica, Vol 106, Iss 12 (2020)
Publication Year :
2020
Publisher :
Ferrata Storti Foundation, 2020.

Abstract

Selinexor is a selective inhibitor of nuclear export with anti-cancer properties. We performed a phase I study to determine the safety and maximum tolerated dose of selinexor when combined with high-dose dexamethasone, ifosfamide, carboplatin and etoposide (DICE) in relapsed/refractory T-cell lymphoma (TCL) and natural-killer/T-cell lymphoma (NKTL). Patients with relapsed/refractory TCL and NKTL were treated with standard dose ICE, dexamethasone 20 mg on days 3 to 7, and escalating doses of oral selinexor on days 3, 5 and 7 in a 3+3 design. Dose levels (DL) 1, 2 and 3 were 40, 60 and 80 mg, respectively. Eleven patients with a median age of 60 years were enrolled; six at DL1 and five at DL2. Patients had received a median of two (range, 1-4) prior lines of treatment and seven had primary refractory disease at entry into the study. Patients received a median of three cycles (range, 1-6) of selinexor-DICE. The most common grade 1 or 2 toxicities included nausea (64%), fatigue (55%), and anorexia (45%) and the most common grade 3 or 4 toxicities included thrombocytopenia (82%), anemia (82%), neutropenia (73%), and hyponatremia (73%). Two patients developed dose-limiting toxicities at DL2 and one at DL1. Five patients discontinued treatment for reasons other than disease progression or lack of response. Of the ten evaluable patients, the overall and complete response rates were 91% and 82%, respectively. The maximum tolerated dose of selinexor was 40 mg when combined with DICE. The combination showed promising complete response rates in patients with relapsed/refractory TCL and NKTL but was poorly tolerated. (clinicaltrials. gov identifier: NCT03212937).

Details

Language :
English
ISSN :
03906078 and 15928721
Volume :
106
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Haematologica
Publication Type :
Academic Journal
Accession number :
edsdoj.6c1ddc15724a4725a245f1bd03b47d40
Document Type :
article
Full Text :
https://doi.org/10.3324/haematol.2020.251454