Phase IIA Study of the HDAC Inhibitor ITF2357 in Patients With JAK-2 V617F Positive Chronic Myeloproliferative Diseases
Condition: Myeloproliferative Diseases
MeSH terms: Myeloproliferative Disorders
Intervention: ITF2357
Intervention description: 50 mg b.i.d. PO every day. More precisely, ITF2357 was supplied as 50 mg hard gelatine capsules for oral administration.
Intervention MeSH terms: Givinostat hydrochloride
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 29.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: polycythemia vera (PV); essential thrombocythemia (ET); myelofibrosis (MF)

Summary:

      Primary Objective:

      To evaluate efficacy and safety of ITF2357 in the treatment of patients with JAK2V617F
      positive myeloproliferative diseases [Polycythemia Vera (PV), Essential Thrombocytosis (ET),
      Myelofibrosis (MF)]. Efficacy was evaluated by ad hoc haematological and clinical criteria
      for PV and ET, and by internationally established response criteria (EUMNET criteria) for MF.
      Safety was evaluated by number of subjects experiencing an Adverse Event (AE), type,
      frequency, severity, timing and relatedness of AEs, including changes in vital signs and
      clinical laboratory results.

      Secondary Objective:

      To evaluate the JAK2 mutated allele burden by quantitative Real-Time Polymerase Chain
      Reaction (qRTPCR).
    

Eligibility criteria:

        Inclusion Criteria:

          -  Signed Informed Consent Form

          -  Male or female, age ≥ 18 years

          -  Confirmed diagnosis of PV/ET/MF according to the revised World Health Organisation
             criteria

          -  JAK-2 V617F positivity

          -  In need of cytoreductive therapy when hydroxyurea is not indicated (e.g. young
             patients) or when refractoriness to the drug is documented

        Exclusion Criteria:

          -  Active bacterial or fungal infection requiring antimicrobial treatment on Day 1

          -  Patients of childbearing potential without a negative pregnancy test prior to
             initiation of the study drug

          -  Pregnancy or lactation

          -  A marked baseline prolongation of QT/QTc interval (e.g. repeated demonstration of a
             QTc interval > 450 ms, according to Bazett's correction formula - see appendix G for
             the formula)

          -  The use of concomitant medications that prolong the QT/QTc interval (see appendix F
             for full list)

          -  Concomitant acute coronary syndromes; uncontrolled hypertension

          -  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 Torsade de Pointes (e.g., heart failure,
             hypokalemia, family history of Long QT Syndrome)

          -  Active Epstein Barr Virus (EBV) infection (i.e. positive serology IgM)

          -  Known HIV infection

          -  Active hepatitis B and/or C infection

          -  History of other disease, metabolic dysfunction, physical examination finding, or
             clinical laboratory finding 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 subject at high risk from treatment
             complications

          -  Eastern Cooperative Oncology Group (ECOG) performance status 3 or greater

          -  Platelets count <100x109/L within 14 days before enrolment

          -  Absolute neutrophil count <1.2x109/L within 14 days before enrolment

          -  Percentage of blast cells in peripheral blood >10% within 14 days before enrolment

          -  Serum creatinine >2xULN (Upper limit of normal)

          -  Total serum bilirubin >1.5xULN

          -  Serum AST (aspartate aminotransferase) / ALT (alanine aminotransferase) > 3xULN

          -  Interferon alpha within 14 days before enrolment

          -  Hydroxyurea within 14 days before enrolment

          -  Anagrelide within 7 days before enrolment

          -  Any other investigational drug within 28 days before enrolment