Long-term Study Evaluating the Effect of Givinostat in Patients With Chronic Myeloproliferative Neoplasms

Overview

This is a multicenter, open label, long-term study testing the long-term safety, tolerability and efficacy of givinostat in patients with Polycythemia Vera, Essential Thrombocythemia, primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis following core protocols in chronic myeloproliferative neoplasms and/or patient-named compassionate use program (if regulated/allowed by the local regulations, e.g. for Italy D.M. 8/5/2003 "Uso terapeutico di medicinale sottoposto a sperimentazione clinica" published on G.U. n. 173 of 28 July 2003, and the following amendments). Patients will continue at their last tolerable dose and treatment schedule of givinostat monotherapy. If patients previously received givinostat in combination with other drugs during a core protocol or a compassionate use program (if regulated/allowed by the local regulations, e.g. for Italy D.M. 8/5/2003 "Uso terapeutico di medicinale sottoposto a sperimentazione clinica" published on G.U. n. 173 of 28 July 2003, and the following amendments), they will be treated at the last tolerable dose of the combination. Assessment of safety and efficacy will be performed at each quarterly visit and each visit will also include laboratory tests and ECG examination. During the visits the clinical benefit will be assessed by Investigator according to the revised European LeukemiaNet response criteria (for PV and ET) and EUMNET response criteria (for MF). The dose of Givinostat will be modified for protocol specified toxicities. The treatment may continue up to Marketing Authorization of givinostat, currently planned in the next 5 years (note: only for Germany, this long-term study is initially limited up to 2 years of treatment). Patients may discontinue study treatment at any time and remain on study therapy as long as they derive clinical benefit. Safety will be monitored at each visit throughout the entire duration of the study. In case the approved label will not cover the whole study population, givinostat will be provided by the Sponsor to those patients not fulfilling the criteria for the approved label of the drug that are still deriving benefit from givinostat at the time of its commercial availability.

This is a multicenter, open label, long-term study testing the long-term safety, tolerability and efficacy of givinostat in patients with PV, ET, primary MF, Post-PV MF, Post-ET MF following core protocols in cMPN (i.e. Study DSC/07/2357/28, Study DSC/08/2357/38, Study DSC/12/2357/45 and/or all further core protocols in cMPN), and/or patient-named compassionate use program (if regulated/allowed by the local regulations, e.g. for Italy D.M. 8/5/2003 "Uso terapeutico di medicinale sottoposto a sperimentazione clinica" published on G.U. n. 173 of 28 July 2003, and the following amendments). Eligible patients will have tolerated previous givinostat treatment and achieved a clinical benefit at the end of the core protocols; alternatively, eligible patients are participating in compassionate use program (if regulated/allowed by the local regulations, e.g. for Italy D.M. 8/5/2003 "Uso terapeutico di medicinale sottoposto a sperimentazione clinica" published on G.U. n. 173 of 28 July 2003, and the following amendments). In addition, patients must have tolerated previous givinostat treatment and achieved a clinical benefit at the end of core protocols or compassionate use program with givinostat, assessed by the Investigator according to the revised clinico-haematological ELN response criteria (for PV and ET) and EUMNET response criteria (for MF). After providing informed written consent before undertaking any protocol-related procedure, an unique patient identification code (patient ID) will be assigned to each patient, will identify the patient throughout his/her participation in the study and can never be reused in case of premature drop-out. Patients will continue at their last tolerable dose and treatment schedule of givinostat monotherapy. If patients previously received givinostat in combination with other drugs (e.g. hydroxyurea) during a core protocol or a compassionate use program , they will be treated at the last tolerable dose of the combination. In general, the dose of study drug may not be increased during this study. However, since the Maximum Tolerated Dose (MTD) of givinostat as chronic treatment has been recently identified and proven tolerable in Polycythenia Vera patients (i.e. 100 mg b.i.d.), selected patients may be eligible for escalation of their givinostat dose up to this level upon consultation with and written permission by Italfarmaco S.p.A. or its designee. Assessment of safety and efficacy will be performed at each quarterly visit and each visit will also include laboratory tests and ECG examination. During the visits the clinical benefit will be assessed by Investigator according to the revised clinico-haematological ELN response criteria (for PV and ET) and EUMNET response criteria (for MF). Patients will be considered for continued treatment on the basis of their clinical response: * if patients continue to derive clinical benefit from participating in the study, they will be allowed to continue study medication; * if patients do not derive clinical benefit from participating in the study, they will discontinue study treatment. For patients who previously participated in a compassionate use program with Givinostat the decision to continue treatment will be based on the assessment of continued clinical benefit derived from study therapy. Of note, since this is a long-term study, at each quarterly visit the Investigator should include in his/her clinical evaluation the patient's benefit-risk assessment, taking into account both the clinical course of the patient in the Study until the visit time (i.e. the "clinical benefit", as above defined in this paragraph) and also any possible treatment option available at the time when the visit is performed. The dose of givinostat will be modified for protocol specified toxicities. The treatment may continue up to Marketing Authorization of Givinostat, currently planned in the next 5 years (note: only for Germany, this long-term study is initially limited up to 2 years of treatment). Patients may discontinue study treatment at any time and remain on study therapy as long as they derive clinical benefit. Safety will be monitored at each visit throughout the entire duration of the study. Treatment will be administered on an outpatient basis and patients will be followed regularly with physical and laboratory tests, as specified in the protocol; in case of hospitalization, the treatment will be continued or interrupted according to the Investigators' decision. In case the approved label will not cover the whole study population, givinostat will be provided by the Sponsor to those patients not fulfilling the criteria for the approved label of the drug that are still deriving benefit from Givinostat at the time of its commercial availability.