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

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

Research output: Contribution to journalArticle

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discontinuation were disease progression (n = 6), grade 2 thrombocytopenia (n = 1), psychiatric symptoms (n = 1) and withdrawn consent (n = 2).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

Original languageEnglish
Pages (from-to)446-455
Number of pages10
JournalBritish Journal of Haematology
Volume150
Issue number4
DOIs
Publication statusPublished - Aug 2010

Keywords

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

ASJC Scopus subject areas

  • Hematology

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    Rambaldi, A., Dellacasa, C. M., Finazzi, G., Carobbio, A., Ferrari, M. L., Guglielmelli, P., Gattoni, E., Salmoiraghi, S., Finazzi, M. C., Di Tollo, S., D'Urzo, C., Vannucchi, A. M., Barosi, G., & Barbui, T. (2010). A pilot study of the Histone-Deacetylase inhibitor Givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms. British Journal of Haematology, 150(4), 446-455. https://doi.org/10.1111/j.1365-2141.2010.08266.x