Long-term Study Evaluating the Effect of Givinostat in Patients With JAK2V617F Positive Chronic Myeloproliferative Neoplasms

Inclusion Criteria:

1. Patients must have completed Givinostat treatment on at least one core study in cMPN (i.e. Study DSC/07/2357/28, Study DSC/08/2357/38 and/or any further core protocols in cMPN), or Patients must be participating in a compassionate use program with Givinostat;
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 JAK2 V617F positive cMPN according to the revised WHO criteria;
4. Patients must have an Eastern Cooperative Oncology Group (ECOG) 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 QTc prolongation at baseline (e.g. repeated demonstration of a QTc interval > 450 ms);
4. Use of concomitant medications known to prolong the QTc interval;

5. Clinically significant cardiovascular disease including:

   • Uncontrolled hypertension, myocardial infarction, unstable angina within 6 months from study start;
   • New York Heart Association (NYHA) 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 TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
6. History of virus infection including HIV, HBV and HCV;
7. Platelets count < 100 x109/L within 14 days before enrolment;
8. Absolute neutrophil count < 1.2 x109/L within 14 days before enrolment;
9. Serum creatinine > 2 xULN;
10. Total serum bilirubin > 1.5 xULN;
11. Serum AST/ALT > 3 xULN;
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;
14. Patients with known hypersensitivity to the components of potential study therapy.