A phase II study of Givinostat in combination with hydroxycarbamide in patients with polycythaemia vera unresponsive to hydroxycarbamide monotherapy

被引：106

作者：

Finazzi, Guido ^{[1
]}

Vannucchi, Alessandro M. ^{[2
]}

Martinelli, Vincenzo ^{[3
]}

Ruggeri, Marco ^{[4
]}

Nobile, Francesco ^{[5
]}

Specchia, Giorgina ^{[6
]}

Pogliani, Enrico Maria ^{[7
]}

Olimpieri, Odoardo Maria ^{[8
]}

Fioritoni, Giuseppe ^{[9
]}

Musolino, Caterina ^{[10
]}

Cilloni, Daniela ^{[11
]}

Sivera, Piera ^{[12
]}

Barosi, Giovanni ^{[13
]}

Finazzi, Maria Chiara ^{[1
]}

Di Tollo, Silvia ^{[14
]}

Demuth, Tim ^{[14
]}

Barbui, Tiziano ^{[1
]}

Rambaldi, Alessandro ^{[1
]}

机构：

[1] Osped Papa Giovanni XXIII, Bergamo, Italy

[2] Univ Florence, AOU Careggi, Florence, Italy

[3] AOU Federico II, Haematol Unit, Naples, Italy

[4] San Bortolo Hosp, Dept Cell Therapy & Haematol, Vicenza, Italy

[5] AO Bianchi Melacrino Morelli, Oncohaematol Dept, Reggio Di Calabria, Italy

[6] AOU Policlin Consorziale, Haematol Unit, Bari, Italy

[7] Univ Milano Bicocca, New Hosp San Gerardo, Monza, Italy

[8] Campus Biomed Univ, Dept Haematol, Rome, Italy

[9] AUSL Spirito Santo, Clin Haematol Unit, Pescara, Italy

[10] Azienda Osped Univ, UOC Haematol, Messina, Italy

[11] AOU San Luigi Gonzaga, Orbassano, Italy

[12] AO Ordine Mauriziano Umberto I, SCU Haematol, Turin, Italy

[13] IRCCS Policlin S Matteo Fdn, Ctr Study Myelofibrosis, Pavia, Italy

[14] Italfarmaco SpA, Clin R&D Dept, Cinisello Balsamo, Italy

来源：

BRITISH JOURNAL OF HAEMATOLOGY | 2013年 / 161卷 / 05期

关键词：

Givinostat; histone-deacetylase inhibitor; hydroxycarbamide; polycythaemia vera; myeloproliferative neoplasm; DEACETYLASE INHIBITOR ITF2357; MYELOPROLIFERATIVE NEOPLASMS; PRIMARY MYELOFIBROSIS; ANTILEUKEMIC ACTIVITY; HISTONE; RUXOLITINIB; CRITERIA; THERAPY; CELLS;

D O I：

10.1111/bjh.12332

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 100mg/d) in combination with MTD of HC. The European LeukaemiaNet response criteria were used to assess the primary endpoint after 12weeks of treatment. Complete or partial response was observed in 55% and 50% of patients receiving 50 or 100mg of Givinostat, respectively. Control of pruritus was observed in 64% and 67% of patients in the 50 and 100mg 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 center dot 5%) in each treatment arm. The combined use of Givinostat and HC was safe and clinically effective in HC-unresponsive PV patients.

引用

页码：688 / 694

页数：7

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