title: 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discontinuation were disease progression (n = 6), grade 2 thrombocytopenia (n = 1), psychiatric symptoms (n = 1) and withdrawn consent (n = 2).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.
authors.affiliation: Haematology, Ospedali Riuniti Di Bergamo, Largo Barozzi, Bergamo, Italy. arambaldi@ospedaliriuniti.bergamo.it
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
authors.forename: Chiara Maria
authors.initials: CM
authors.lastname: Dellacasa
authors.forename: Guido
authors.initials: G
authors.lastname: Finazzi
authors.forename: Alessandra
authors.initials: A
authors.lastname: Carobbio
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Ferrari
authors.forename: Paola
authors.initials: P
authors.lastname: Guglielmelli
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gattoni
authors.forename: Silvia
authors.initials: S
authors.lastname: Salmoiraghi
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Finazzi
authors.forename: Silvia
authors.initials: S
authors.lastname: Di Tollo
authors.forename: Carmine
authors.initials: C
authors.lastname: D'Urzo
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barosi
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
mesh_terms: D000328:Adult; D000368:Aged; D004334:Drug Administration Schedule; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D006877:Hydroxamic Acids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D053614:Janus Kinase 2 / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009196:Myeloproliferative Disorders / Q000188:drug therapy* / Q000235:genetics; D010865:Pilot Projects; D011087:Polycythemia Vera / Q000188:drug therapy / Q000235:genetics; D055728:Primary Myelofibrosis / Q000188:drug therapy / Q000235:genetics; D013920:Thrombocythemia, Essential / Q000188:drug therapy / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; C507924:JAK2 protein, human; D053614:Janus Kinase 2; C502418:givinostat hydrochloride