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

作者：Rambaldi Alessandro^*; Dellacasa Chiara Maria; Finazzi Guido; Carobbio Alessandra; Ferrari Maria Luisa; Guglielmelli Paola; Gattoni Elisabetta; Salmoiraghi Silvia; Finazzi Maria Chiara; Di Tollo Silvia; D'Urzo Carmine; Vannucchi Alessandro M; Barosi Giovanni; Barbui Tiziano

来源：British Journal of Haematology, 2010, 150(4): 446-455.

DOI：10.1111/j.1365-2141.2010.08266.x

• Polycythaemia Vera
• Essential Thrombocythaemia
• Myelofibrosis
• HDAC inhibitors
• Givinostat

P>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discontinuation were disease progression (n = 6), grade 2 thrombocytopenia (n = 1), psychiatric symptoms (n = 1) and withdrawn consent (n = 2).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.

• 出版日期2010-8