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

NCT00606307 | Completed Phase 2 Results

• 1 other identifier: DSC/07/2357/28
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 2

Brief 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).

Conditions

Myeloproliferative Diseases

Keywords

polycythemia vera (PV); essential thrombocythemia (ET); myelofibrosis (MF)

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Objective Responses (Complete, Major, Moderate or Minor Responses), in Terms of Best Overall Response

  Patients with Objective Response were defined as those patients achieving a complete, major, moderate or minor (only for Myelofibrosis patients) response during the experimental treatment course. The "best response" is reported hereunder by intensity of response.

  Every single week from week 1 to week 24 of treatment

Secondary Outcomes (2)

• Change in JAK2 Mutated Allele Burden

  At screening, at week 12, at week 24, at the end of treatment (EOT) visit

• Number of Subject Experiencing an Adverse Event

  At weekly visits (Days 8, 15, 22, 36, 43, 50, 64, 71, 78, 99, 127, 155); At monthly visits (Days 29, 57, 85 113, 141,169); at end of treatment visit

Study Arms (1)

ITF2357

EXPERIMENTAL

Initial dose of 50 mg b.i.d. that was subsequently escalated to 50 mg t.i.d in case of lack of significant toxicity.

Drug: ITF2357

Interventions

ITF2357 DRUG

50 mg b.i.d. PO every day. More precisely, ITF2357 was supplied as 50 mg hard gelatine capsules for oral administration.

Also known as: Givinostat

ITF2357

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Italfarmaco: lead

Study Sites (2)

Ospedali riuniti

Bergamo, 24158, Italy

Location

IRCCS - Pol. San Matteo

Pavia, 27100, Italy

Location

MeSH Terms

Conditions

Polycythemia Vera; Thrombocythemia, Essential; Primary Myelofibrosis

Interventions

givinostat hydrochloride; givinostat

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Limitations and Caveats

Non reported

Results Point of Contact

• Title: Tiziano Oldoni, MD
• Organization: Italfarmaco S.p.A.

t.oldoni@italfarmaco.com

+39 02 6443

Study Officials

• tiziano oldoni, MD

  Italfarmaco

  STUDY DIRECTOR

• Alessandro Rambaldi, MD

  A.O. Ospedale Papa Giovanni XXIII

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 21, 2008
• First Posted: February 1, 2008
• Study Start: December 1, 2007
• Primary Completion: December 1, 2008
• Study Completion: December 1, 2008
• Last Updated: December 3, 2019
• Results First Posted: December 3, 2019

Record last verified: 2019-11

Locations

IT (2)