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: Guido Finazzi, Alessandro M Vannucchi, Vincenzo Martinelli, Marco Ruggeri, Francesco Nobile, Giorgina Specchia, Enrico Maria Pogliani, Odoardo Maria Olimpieri, Giuseppe Fioritoni, Caterina Musolino, Daniela Cilloni, Piera Sivera, Giovanni Barosi, Maria Chiara Finazzi, Silvia Di Tollo, Tim Demuth, Tiziano Barbui, Alessandro Rambaldi
• Journal: British journal of haematology (Br J Haematol) Vol. 161 Issue 5 Pg. 688-694 (Jun 2013) ISSN: 1365-2141 [Electronic] England
• PMID: 23573950 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)
• Copyright: © 2013 John Wiley & Sons Ltd.

Chemical References

• Carbamates
• Histone Deacetylase Inhibitors
• Nucleic Acid Synthesis Inhibitors
• givinostat
• Hydroxyurea

Topics

• Adult
• Aged
• Aged, 80 and over
• Carbamates (administration & dosage, adverse effects, therapeutic use)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Therapy, Combination
• Female
• Histone Deacetylase Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Humans
• Hydroxyurea (administration & dosage, adverse effects, therapeutic use)
• Male
• Middle Aged
• Nucleic Acid Synthesis Inhibitors (administration & dosage, adverse effects, therapeutic use)
• Polycythemia Vera (drug therapy)
• Treatment Failure
• Treatment Outcome