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.
Name: Givinostat
Description: To obtain information on the long-term efficacy of Givinostat in patients with chronic myeloproliferative neoplasms following core protocols or compassionate use program: Number of patients experiencing adverse events; Type, incidence, and severity of treatment-related adverse events. To determine the long term safety and tolerability of Givinostat in patients with chronic myeloproliferative neoplasms following core protocols or compassionate use program: For Polycythemia Vera and Essential Thrombocythemia, Complete response and partial response rate according to the revised clinico-haematological European LeukemiaNet response criteria; For Myelofibrosis, complete response, major response, moderate response and minor response rate according to European Myelofibrosis Network response criteria. Note that these assessment will be repeated periodically (each 3 months) during the study. In fact, the treatment will continue up to Marketing Authorisation of Givinostat.
Measure: Long-term safety and efficacy Time: 3 monthsDescription: To evaluate the effect of Givinostat on each single response parameter according to the revised European LeukemiaNet (for Polycythemia Vera and Essential Thrombocythemia) and European European Myelofibrosis Network response criteria (for Myelofibrosis). Note that this assessment will be repeated periodically (each year) during the study. In fact, the treatment will continue up to Marketing Authorisation of Givinostat.
Measure: Clinical exploratory endpoint Time: 1 yearDescription: To evaluate the molecular response (i.e. reduction of the allele burden of the mutated Janus Kinase 2 in the position V617F). Note that this assessment will be repeated periodically (each year) during the study. In fact, the treatment will continue up to Marketing Authorisation of Givinostat.
Measure: Molecular exploratory endpoint Time: 1 yearDescription: To identify potential other markers predictive of clinical benefit of Givinostat (e.g. potential pharmacodynamic markers). Note that this assessment will be repeated periodically (each year) during the study. In fact, the treatment will continue up to Marketing Authorisation of Givinostat.
Measure: Biomolecular exploratory endpoint Time: 1 yearAllocation: N/A
Single Group Assignment
There is one SNP
reduction of the allele burden of the mutated Janus Kinase 2 in the position V617F). --- V617F ---