JAK2V617F positive Polycythemia Vera MedDRA version: 14.1 Level: LLT Classification code 10036061 Term: Polycythemia vera System Organ Class: 100000004864
Conditions
Interventions
Product Name: Givinostat
Product Code: ITF2357
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: GIVINOSTAT
Other descriptive name: ITF2357
Concentration unit: mg milligram(s)
Concentration type
Sponsors
ITALFARMACO S.p.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must be able to provide informed consent and be willing to sign an informed consent form; 2. Patients must have an age =18 years; 3. Patients must have a confirmed diagnosis of PV according to the revised WHO criteria; 4. Patients must have JAK2V617F positive disease; 5. Patients must have an active/not controlled disease defined as a) HCT = 45% or HCT 400 x109/L, and c) WBC > 10 x109/L; Note that if the enrolment in Part A is slow (i.e. 600 x109/L; b) MF patients: no response according to EUMNET criteria. 6. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status = 1 in Part A, ECOG performance status = 2 in Part B within 7 days of initiating study drug; 7. Female patient of childbearing potential has a negative serum or urine pregnancy test within 72 hours of the first dose of study therapy; please note that a borderline urine pregnancy test must be followed with a serum pregnancy test; 8. Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential; 9. Adequate and acceptable organ function within 7 days of initiating study drug; 10. Willingness and capability to comply with the requirements of the study. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 22
Exclusion criteria
Exclusion criteria: 1. Active bacterial or mycotic infection requiring antimicrobial treatment; 2. Pregnancy or nursing; 3. A clinically significant QTc prolongation at baseline (e.g. repeated demonstration of a QTc interval = 450 msec); 4. Use of concomitant medications known to prolong the QT/QTc interval; 5. Clinically significant cardiovascular disease including: a) Uncontrolled hypertension despite medical treatment, myocardial infarction, unstable angina within 6 months from study start; b) New York Heart Association (NYHA) Grade II or greater congestive heart failure; c) History of any cardiac arrhythmia requiring medication (irrespective of its severity); d) A history of additional risk factors for TdP (e.g. heart failure, hypokalemia, family history of Long QT Syndrome); 6. Known positivity for HIV; 7. Known active HBV and/or HCV infection; 8. Platelet count 2 xULN; 11. Total serum bilirubin > 1.5 xULN except in case of Gilbert’s disease; 12. Serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) > 3 x ULN; 13. History of other diseases (including active tumours), 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; 14. Prior treatment with a JAK2 or HDAC inhibitor or participation in an interventional clinical trial for cMPN, including PV, ET or MF; 15. Systemic treatment for cMPN other than aspirin/cardio aspirin; 16. Hydroxyurea within 28 days before enrolment (i.e. the receipt of the Patient ID); 17. Interferon alpha within 14 days before enrolment (i.e. the receipt of the Patient ID); 18. Anagrelide within 7 days before enrolment (i.e. the receipt of the Patient ID); 19. Any other investigational drug or device within 28 days before enrolment (i.e. the receipt of the Patient ID); 20. Patient with known hypersensitivity to the components of study therapy.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Part A • To characterize the safety, tolerability and MTD of Givinostat in patients with PV. Part B • To evaluate the preliminary efficacy of Givinostat at the MTD after 3 cycles. • To determine the safety and tolerability of Givinostat at the MTD after 3 cycles. ;Secondary Objective: Part A • To evaluate the preliminary efficacy of Givinostat after 3 and 6 cycles of treatment. • To characterize PK. Part B • To evaluate the preliminary efficacy of Givinostat at the MTD after 6 cycles. • To determine the safety and tolerability of Givinostat at the MTD after 6 cycles. • To characterize PK. ;Timepoint(s) of evaluation of this end point: Part A Safety - ongoing MTD - cycle 1 Part B After 3 cycles;Primary end point(s): Part A • Safety and tolerability evaluated as following: - Number of patients experiencing adverse events; - Type, incidence, and severity of treatment-related adverse events, graded according to Common Terminology Criteria for Adverse Events (CTCAE v. 4.03, 14th June 2010). • Determination of the MTD of Givinostat based on cycle 1 DLT’s. Part B • Overall response rate - i.e. Complete Response (CR) and Partial Response (PR) - of Givinostat at the MTD after 3 cycles; the response will be evaluated according to the clinico-haematological European LeukemiaNet (ELN) response criteria. • Safety and tolerability of Givinostat at the MTD after 3 cycles evaluated as following: - Number of patients experiencing adverse events; - Type, incidence, and severity of treatment-related adverse events, graded according to CTCAE v. 4.03. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Part A • Overall response rate - i.e. Complete Response (CR) and Partial Response (PR) - of Givinostat at the MTD after 3 and 6 cycles; the response will be evaluated according to the clinico-haematological ELN response criteria. • Individual Givinostat concentrations tabulated by dose cohort along with descriptive statistics. Part B • Overall response rate - i.e. Complete Response (CR) and Partial Response (PR) - of Givinostat at the MTD after 6 cycles; the response will be evaluated according to the clinico-haematological ELN response criteria. • Safety and tolerability of Givinostat at the MTD after 6 cycles evaluated as following: - Number of patients experiencing adverse events; - Type, incidence, and severity of treatment-related adverse events, graded according to CTCAE v. 4.03. • Individual Givinostat concentrations tabulated with descriptive statistics. ;Timepoint(s) of evaluation of this end point: Part A cycle 3 and cycle 6 Part B Cycle 6 | — |
Countries
France, Germany, Hungary, Italy, Poland, United Kingdom
Contacts
Public ContactPaolo Bettica
Italfarmarmaco S.p.A.
Outcome results
None listed