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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00606307
Recruitment Status : Completed
First Posted : February 1, 2008
Last Update Posted : May 24, 2013
Information provided by (Responsible Party):

Brief 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)

Condition or disease Intervention/treatment Phase
Myeloproliferative Diseases Drug: ITF2357 Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 29 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IIA Study of the Histone-deacetylase Inhibitor ITF2357 in Patients With JAK-2 V617F Positive Chronic Myeloproliferative Diseases
Study Start Date : December 2007
Actual Primary Completion Date : December 2008
Actual Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Experimental: ITF2357 Drug: ITF2357
50 mg b.i.d. PO every day

Primary Outcome Measures :
  1. Efficacy evaluated by ad hoc haematological and clinical criteria for PV and ET, and by internationally established response criteria for MF. Safety evaluated by number of subjects experiencing an AE [ Time Frame: 3 months ]

Secondary Outcome Measures :
  1. evaluate the JAK2 mutated allele burden by quantitative RT PCR [ Time Frame: 3 months ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00606307

Ospedali riuniti
Bergamo, Italy, 24158
IRCCS - Pol. San Matteo
Pavia, Italy, 27100
Sponsors and Collaborators
Study Director: tiziano oldoni, MD Italfarmaco
Principal Investigator: Alessandro Rambaldi, MD A.O. Ospedale Papa Giovanni XXIII

Responsible Party: Italfarmaco Identifier: NCT00606307     History of Changes
Other Study ID Numbers: DSC/07/2357/28
First Posted: February 1, 2008    Key Record Dates
Last Update Posted: May 24, 2013
Last Verified: April 2009

Additional relevant MeSH terms:
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Histone Deacetylase Inhibitors
Givinostat hydrochloride
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action