Polycythemia Vera MedDRA version: 14.1 Level: HLT Classification code 10018847 Term: Haematological disorders System Organ Class: 100000004851
Conditions
Interventions
Product Name: GIVINOSTAT
Product Code: ITF2357
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: C1-inhibitor
Concentration unit: mg milligram(s)
Concentration number: 50-
Sponsors
ITALFARMACO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Written Informed Consent. Age ≥18 years. Confirmed diagnosis of Polycythemia Vera according to the revised WHO criteria. JAK2V617F positivity. Non-response to the maximum tolerated dose of hydroxyurea monotherapy for at least 3 months. ECOG performance status =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Active bacterial or mycotic infection requiring antimicrobial treatment. 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). Use of concomitant medications that prolong the QT/QTc interval. Clinically significant cardiovascular disease including: - Uncontrolled hypertension, myocardial infarction, unstable angina within 6 months from study start; - 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). Positive blood test for HIV. Active HBV and/or HCV infection. Platelets count 2xULN. Total serum bilirubin >1.5xULN. Serum AST/ALT > 3xULN. History of other diseases, metabolic dysfunctions, physical examination findings, or clinical laboratory findings 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. Interferon alpha within 14 days before enrolment. Anagrelide within 7 days before enrolment. Any other investigational drug within 28 days before enrolment.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of GIVINOSTAT (ITF2357) in combination with hydroxyurea in patients with JAK2V617F positive Polycythemia Vera non-responders to the maximum tolerated dose of hydroxyurea monotherapy;Primary end point(s): Overall response rate (partial and complete responses) at week 12.;Secondary Objective: - To evaluate the safety and tolerability of GIVINOSTAT (ITF2357) in combination with hydroxyurea in patients with JAK2V617F positive Polycythemia Vera non-responders to the maximum tolerated dose of hydroxyurea monotherapy. - To explore the impact in terms of efficacy and tolerability of GIVINOSTAT (ITF2357) 50 mg dose escalation in patients not achieving at least a partial response at the time when the primary endpoint is assessed (week 12). - To evaluate the molecular response (JAK2 mutated allele burden) by quantitative RT-PCR. - To evaluate the reduction of the fraction of JAK2V617F positive clonogenic progenitors. | — |
Countries
Italy
Outcome results
None listed