Phase II Study of Histone-deacetylase Inhibitor ITF2357 in Refractory/Relapsed Lymphocytic Leukemia

This is an open label, un-controlled, phase II, pilot clinical trial testing ITF2357 in a population of CLL patients relapsed after or refractory to conventional chemotherapy or relapsed after autologous bone marrow transplantation.

Patient received ITF 2357 orally at the dose of 100 mg x 2/die for three months with subsequent dose modifications if requested by the patient's conditions.

The study was prematurely discontinued due to recruitment problems. Since February 2008, date of first patient's first visit, until April 2009, date of early study discontinuation, only 3 patients were enrolled. The Sites involved in the study were 6 but only two actively recruited patients.

CLL is the most frequent type of leukemia in the western world and affects mainly elderly individuals, although about one third of patients are less than 60 years of age at diagnosis.

CLL is a heterogeneous disease characterised by a surprisingly diverse clinical course with patients that may have an overall survival time ranging from months to decades.

CLL accounts for approximately 7000 new cases and 4500 deaths per year in the US.

Chemotherapeutic treatment of CLL is largely ineffective and despite new emerging therapies, CLL still remains an incurable disease.

ITF 2357 is a novel and proprietary molecule synthesized by Italfarmaco S.p.A. Research Laboratories, provided with an established and powerful HDAC-inhibitory activity (see below for further details). It is being developed for a range of possible clinical applications both in oncohaematological conditions and in chronic inflammatory diseases. The former application is consistent with the well known antitumor pharmacological properties of HDAC-inhibitors as a family (i.e. cell-cycle arrest, pro-apoptotic and cell-differentiating effects); the latter application (chronic inflammation) is based of the demonstrated anticytokine effect of ITF 2357.