title: A phase II study of Givinostat in combination with hydroxycarbamide in patients with polycythaemia vera unresponsive to hydroxycarbamide monotherapy.
abstract: Givinostat, a histone-deacetylase inhibitor (HDACi), inhibits proliferation of cells bearing the JAK2 V617F mutation and has shown significant activity with good tolerability in patients with chronic myeloproliferative neoplasms (MPN). In this multicentre, open-label, phase II study, 44 patients with polycythaemia vera (PV), unresponsive to the maximum tolerated doses (MTD) of hydroxycarbamide (HC), were treated with Givinostat (50 or 100 mg/d) in combination with MTD of HC. The European LeukaemiaNet response criteria were used to assess the primary endpoint after 12 weeks of treatment. Complete or partial response was observed in 55% and 50% of patients receiving 50 or 100 mg of Givinostat, respectively. Control of pruritus was observed in 64% and 67% of patients in the 50 and 100 mg groups, respectively. The combination of Givinostat and HC was well tolerated: eight patients (18%) discontinued, four in each treatment arm; grade 3 adverse events were reported in one patient (4·5%) in each treatment arm. The combined use of Givinostat and HC was safe and clinically effective in HC-unresponsive PV patients.
authors.affiliation: Haematology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Guido
authors.initials: G
authors.lastname: Finazzi
authors.affiliation: Haematology, University of Florence, A.O.U. Careggi, Florence, Italy.
authors.forename: Alessandro M
authors.initials: AM
authors.lastname: Vannucchi
authors.affiliation: Haematology Unit, A.O.U. "Federico II", Naples, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Martinelli
authors.affiliation: Department of Cell Therapy and Haematology, San Bortolo Hospital, Vicenza, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Ruggeri
authors.affiliation: Onco-haematology Department, A.O. "Bianchi-Melacrino-Morelli, Reggio Calabria, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Nobile
authors.affiliation: Haematology Unit, A.O.U. Policlinico Consorziale, Bari, Italy.
authors.forename: Giorgina
authors.initials: G
authors.lastname: Specchia
authors.affiliation: Clinical Haematology, New Hospital San.Gerardo, University of Milano Bicocca, Monza, Italy.
authors.forename: Enrico Maria
authors.initials: EM
authors.lastname: Pogliani
authors.affiliation: Haematology Department, "Campus Bio-Medico" University, Rome, Italy.
authors.forename: Odoardo Maria
authors.initials: OM
authors.lastname: Olimpieri
authors.affiliation: Clinical Haematology Unit, AUSL "Spirito Santo", Pescara, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fioritoni
authors.affiliation: UOC Haematology, Azienda Ospedaliera Universitaria, Messina, Italy.
authors.forename: Caterina
authors.initials: C
authors.lastname: Musolino
authors.affiliation: Internal Medicine 2, AOU San Luigi Gonzaga, Orbassano, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Cilloni
authors.affiliation: SCU Haematology, A.O. "Ordine Mauriziano" Umberto I, Turin, Italy.
authors.forename: Piera
authors.initials: P
authors.lastname: Sivera
authors.affiliation: Centre for the Study of Myelofibrosis, IRCCS Policlinico S.Matteo Foundation, Pavia, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Barosi
authors.affiliation: Haematology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Finazzi
authors.affiliation: Clinical R&D Department, Italfarmaco S.p.A., Cinisello Balsamo, Italy.
authors.forename: Silvia Di
authors.initials: SD
authors.lastname: Tollo
authors.affiliation: Clinical R&D Department, Italfarmaco S.p.A., Cinisello Balsamo, Italy.
authors.forename: Tim
authors.initials: T
authors.lastname: Demuth
authors.affiliation: Haematology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Tiziano
authors.initials: T
authors.lastname: Barbui
authors.affiliation: Haematology, Ospedale Papa Giovanni XXIII, Bergamo, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Rambaldi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002219:Carbamates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019384:Nucleic Acid Synthesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011087:Polycythemia Vera / Q000188:drug therapy*; D017211:Treatment Failure; D016896:Treatment Outcome
chemical_list: D002219:Carbamates; D056572:Histone Deacetylase Inhibitors; D019384:Nucleic Acid Synthesis Inhibitors; C575255:givinostat; D006918:Hydroxyurea