A pilot study of the Histone-Deacetylase inhibitor Givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms.

Abstract:

:A phase II A study was conducted to evaluate the safety and efficacy of Givinostat, a novel Histone-Deacetylases inhibitor, in patients with Polycythaemia Vera (PV, n = 12), Essential Thrombocythaemia (ET, n = 1) and Myelofibrosis (n = 16), bearing the JAK2V617F mutation. The study was approved by the local ethics committees and all human participants gave written informed consent. Givinostat was given orally for 24 weeks at a starting dose of 50 mg twice daily. The median treatment duration was 20 weeks. Reasons for treatment discontinuation were disease progression (n = 6), grade 2 thrombocytopenia (n = 1), psychiatric symptoms (n = 1) and withdrawn consent (n = 2). A dose reduction was applied in 10 patients while a temporary interruption occurred in 15. Among 13 PV/ET patients, 1 complete, 6 partial and 4 no responses were documented at study end while 2 patients went off-study, prematurely. Three major responses were registered among 16 MF patients. Pruritus disappeared in most patients and reduction of splenomegaly was observed in 75% of PV/ET and 38% of MF patients. Reverse transcription polymerase chain reaction identified a trend to reduction of the JAK2V617F allele burden. Givinostat was well tolerated and could induce haematological response in most PV and some MF patients.

journal_name

Br J Haematol

authors

Rambaldi A,Dellacasa CM,Finazzi G,Carobbio A,Ferrari ML,Guglielmelli P,Gattoni E,Salmoiraghi S,Finazzi MC,Di Tollo S,D'Urzo C,Vannucchi AM,Barosi G,Barbui T

doi

10.1111/j.1365-2141.2010.08266.x

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

446-55

issue

4

eissn

0007-1048

issn

1365-2141

pii

BJH8266

journal_volume

150

pub_type

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