Patient case: 36-year-old female with Brugada syndrome; genetic feature: SCN5A

Clinical trial: Phase IIA Study of the HDAC Inhibitor ITF2357 in Patients With JAK-2 V617F Positive Chronic Myeloproliferative Diseases

Summary: In recent years several reports have documented that Histone Deacetylases (HDACs) inhibitors induce neoplastic cells to undergo growth arrest, differentiation and/or apoptotic cell death. Recently, inhibitors of HDACs has also been shown to inhibit endothelial cell proliferation and angiogenesis in vivo. Several HDAC-inhibitors are currently in clinical trials as novel anticancer agents. Among these agents, ITF2357 has most recently been shown to be a potent inhibitor of the autonomous proliferation of haematopoietic cells from patients with myeloproliferative disorders carrying the JAK2 V617F mutation. The aim of the present study is to evaluate the efficacy and safety of ITF2357 in the treatment of polycythemia vera (PV), essential thrombocythemia (ET) and myelofibrosis (MF)


Eligibility: Inclusion Criteria:
  -  Signed Informed Consent Form
  -  Male or female, age ≥ 18 years
  -  Confirmed diagnosis of PV/ET/MF according to the revised WHO 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 TdP (e.g., heart failure, hypokalemia, family history of Long QT Syndrome)
  -  Active 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
  -  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
  -  Total serum bilirubin >1.5xULN
  -  Serum AST/ALT > 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

Relevance to patient case: not relevant