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

Sponsored by:	Italfarmaco
Information provided by:	Italfarmaco
ClinicalTrials.gov Identifier:	NCT00606307

Purpose

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	Intervention	Phase
Myeloproliferative Diseases	Drug: ITF2357	Phase II

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title:	A Phase IIA Study of the Histone-Deacetylase Inhibitor ITF2357 in Patients With JAK-2 V617F Positive Chronic Myeloproliferative Diseases

Further study details as provided by Italfarmaco:

Primary Outcome Measures:

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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

evaluate the JAK2 mutated allele burden by quantitative RT PCR [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	27
Study Start Date:	December 2007
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	May 2009 (Final data collection date for primary outcome measure)

Intervention Details:

50 mg b.i.d. PO every day

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00606307

Contacts

Contact: tiziano oldoni, MD

+39 02 6443 ext 2540

t.oldoni@italfarmaco.com

Locations

Italy
IRCCS - Pol. San Matteo	Recruiting
Pavia, Italy, 27100
Contact: Giovanni Barosi, MD +39 0382 5036 ext 36 barosig@smatteo.pv.it
Ospedali riuniti	Recruiting
bergamo, Italy, 24158
Contact: alessandro rambaldi, MD +39 035266 ext 808 arambaldi@ospedaliriuniti.bergamo.it
Principal Investigator: alessandro rambaldi, MD

Sponsors and Collaborators

Italfarmaco

Investigators

Study Director:	tiziano oldoni, MD	Italfarmaco
Principal Investigator:	Alessandro Rambaldi, MD	Ospedali Riuniti di Bergamo

More Information

Responsible Party:	italfarmaco ( tiziano oldoni )
Study ID Numbers:	DSC/07/2357/28
Study First Received:	January 21, 2008
Last Updated:	December 15, 2008
ClinicalTrials.gov Identifier:	NCT00606307
Health Authority:	Italy: Ministry of Health

Study placed in the following topic categories:

Hematologic Diseases
Chronic Myeloproliferative Disorders
Myeloproliferative Disorders
Bone Marrow Diseases

ClinicalTrials.gov processed this record on January 16, 2009