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

Inclusion Criteria:

1. Patients must have completed Givinostat treatment on at least one core study in chronic myeloproliferative neoplasms, or patients must be participating in a compassionate use program with Givinostat AND 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);
2. Patients must be able to provide informed consent and be willing to sign an informed consent form;
3. Adult patients (age ≥ 18 years) of both genders with established diagnosis of chronic myeloproliferative neoplasms according to the revised WHO criteria;
4. Patients must have an Eastern Cooperative Oncology Group performance status < 3;
5. Acceptable organ function within 7 days of initiating study drug;
6. Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential;
7. Willingness and capability to comply with the requirements of the study.

Exclusion Criteria:

1. Active bacterial or mycotic infection requiring antimicrobial treatment;
2. Pregnancy or nursing;
3. A clinically significant corrected QT interval prolongation at baseline;
4. Use of concomitant medications known to prolong the corrected QT interval;

5. Clinically significant cardiovascular disease including:

   • Uncontrolled hypertension, myocardial infarction, unstable angina within 6 months from study start;
   • New York Heart Association Grade II or greater congestive heart failure;
   • History of any cardiac arrhythmia requiring medication (irrespective of its severity);
   • A history of additional risk factors for Torsade de Point;
6. History of virus infection including human immuno deficiency, hepatitis B virus and hepatitis C virus;
7. Platelets count < 100 x109/L within 14 days before enrolment (i.e. the receipt of the Patient ID);
8. Absolute neutrophil count < 1.2 x109/L within 14 days before enrolment (i.e. the receipt of the Patient ID);
9. Serum creatinine > 2 times the upper normal limit;
10. Total serum bilirubin > 1.5 times the upper normal limit;
11. Serum Aspartate aminotransferase/Alanine aminotransferase > 3 times the upper normal limit;
12. History of other diseases, metabolic dysfunctions, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that contraindicates use of an investigational drug or that might affect interpretation of the results of the study or render the patient at high risk from treatment complications;
13. Any investigational drug other than Givinostat within 28 days before enrolment (i.e. the receipt of the Patient ID);
14. Patients with known hypersensitivity to the components of potential study therapy.