TY - JOUR
T1 - A pilot study of the Histone-Deacetylase inhibitor Givinostat in patients with JAK2V617F positive chronic myeloproliferative neoplasms
AU - Rambaldi, Alessandro
AU - Dellacasa, Chiara Maria
AU - Finazzi, Guido
AU - Carobbio, Alessandra
AU - Ferrari, Maria Luisa
AU - Guglielmelli, Paola
AU - Gattoni, Elisabetta
AU - Salmoiraghi, Silvia
AU - Finazzi, Maria Chiara
AU - Di Tollo, Silvia
AU - D'Urzo, Carmine
AU - Vannucchi, Alessandro M.
AU - Barosi, Giovanni
AU - Barbui, Tiziano
PY - 2010/8
Y1 - 2010/8
N2 - 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discontinuation were disease progression (n = 6), grade 2 thrombocytopenia (n = 1), psychiatric symptoms (n = 1) and withdrawn consent (n = 2).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.
AB - 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discontinuation were disease progression (n = 6), grade 2 thrombocytopenia (n = 1), psychiatric symptoms (n = 1) and withdrawn consent (n = 2).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.
KW - Essential Thrombocythaemia
KW - Givinostat
KW - HDAC inhibitors
KW - Myelofibrosis
KW - Polycythaemia Vera
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U2 - 10.1111/j.1365-2141.2010.08266.x
DO - 10.1111/j.1365-2141.2010.08266.x
M3 - Article
C2 - 20560970
AN - SCOPUS:77955168425
VL - 150
SP - 446
EP - 455
JO - British Journal of Haematology
JF - British Journal of Haematology
SN - 0007-1048
IS - 4
ER -