Chronic myeloproliferative neoplasm MedDRA version: 20.0 Level: HLT Classification code 10028578 Term: Myeloproliferative disorders (excl leukaemias) System Organ Class: 10005329 - Blood and lymphatic system disorders MedDRA version: 20.0 Level: SOC Classification code 10005329 Term: Blood and lymphatic system disorders System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: Givinostat hydrochloride monohydrate
Product Code: ITF2357
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: Givinostat
CAS Number: 732302-99-7
Other descriptive name: Givinostat h
Sponsors
ITALFARMACO S.p.A
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must have completed Givinostat treatment on at least one core study in cMPN (i.e. Study DSC/07/2357/28, DSC/08/2357/38 and/ or any future core protocols in cMPN), or Patients must be participating in a compassionate use program with Givinostat and Patients must have tolerated previous Givinostat treatment and achieved a clinical benefit at the end of core protocols or compassionate use program with Givinostat, assessed by the Investigator according to the revised clinico-haematological ELN response criteria (for PV and ET) and EUMNET response criteria (for MF) 2. Patients must be able to provide informed consent and be willing to sign an informed consent form 3. Adult patients (age =18 years), of both genders, and with established diagnosis of JAK2V617F positive cMPN according to the revised WHO criteria 4. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Pregnancy or nursing (lactating) women, where pregnancy is defined as the state of a female after conception, confirmed by a positive human Chorionic Gonadotropin (hCG) laboratory test (i.e. >5 mIU/mL) an until the termination of gestation; 2. A clinically significant QTc prolongation at baseline (e.g. repeated demonstration of a QTc interval = 450 msec); Of note, a repeated demonstration of a QTc interval >450 msec means that, if the first ECG evaluation demonstrates a prolonged QTc interval (i.e. a QTc interval = 450 msec), two additional ECG evaluations over a brief period of time (i.e. 5 minutes between each recording) must be performed. The averaged value of these three ECG evaluations has to be used for the evaluation of the QTc interval. In the eCRF all the performed ECG evaluations have to be entered as well as the average value of multiple ECG evaluation, if necessary 3. Use of drugs concomitant medications known to prolong the QTc interval 4. Clinically significant cardiovascular disease including: - Uncontrolled hypertension, myocardial infarction, unstable angina within 6 months of study start; - New York Heart Association (NYHA) grade II or greater congestive heart failure - History of any cardiac arrhythmia requiring medication (regardless of severity) - A history of additional risk factors for TdP (eg, heart failure, hypokalemia, family history of long QTc syndrome) 5. Active virus infection including HIV, HBV and HCV 6. Platelets count 1.5xULN except in case of Gilbert's disease or pattern consistent with Gilbert's disease 9. Serum asparatate aminotransferase / alanine aminotransferase AST/ALT >3xULN 10. Serum Cystatin C > 2 x ULN for two subsequent evaluations (i.e. if the value of serum Cystatin C is > 2 x ULN, the test will be repeated once, and if the value is again > 2 x ULN, this becomes an exclusion criterion). 11. Uncontrolled hypertriglyceridemia at baseline, i.e. triglycerides >1.5xULN in fasting state. 12. History and/or presence of other diseases, metabolic dysfunctions, physical examination findings, or clinical laboratory findings giving reasonable suspicion of a disease or condition that contraindicated use of an investigational drug or that might affect interpretation of the results of the study or might render the patient at high risk from treatment complications or significantly alter the absorption of the study drug 13. Any investigational drug other than givinostat within 28 days before enrolment. Notably . the use of such medicaitons within 28 days or 6 half-lives - whichever is longer - prior to the first dose of study drugs (i.e. Day 1) and during the study through all the study conduct (including any safety follow-up [FU] visit) is prohibited. 14. Use of concomitant medications known to inhibit Pgp 15. Patients with known hypersensitivity to the components of potential study therapy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To determine the long-term safety and tolerability of givinostat in patients with cMPN following core protocols or compassionate use program. • To obtain information on the long-term efficacy of givinostat in patients with cMPN following core protocols or compassionate use program. ;Secondary Objective: • To evaluate the long-term effect of givinostat on single parameters of the PV, ET and MF response criteria • To evaluate the long-term molecular response (JAK2 mutated allele burden) by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) • To identify potential other markers predictive of clinical benefit of givinostat (e.g. potential pharmacodynamics – PD – markers) • To evaluate the disease parameters related to disease evolution and history (e.g. thrombotic rate, progression free survival (PFS) etc.). ;Primary end point(s): Long term safety and tolerability • Number of patients experience 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). Long term efficacy • For PV and ET: Complete response (CR) and partial response (PR) rate according to the revised clinicl-haematological European LeukemiaNet (ELN) response criteria • For MF: complete response, major response, moderate response and minor response rate according to European Myelofibrosis Network (EUMNET) response criteria If the response as per ELN/EUMNET criteria is not evaluable, due to missing or not done evaluations, the missing evaluations should be repeated within one week from the visit in order to calculate the response as per ELN/EUMNET response criteria. Of note, since this is a long-term Study, at each quarterly visit the Investigator should include in their clinical evaluation the patient's benefit-risk assessment, taking into account both the clinical course of the patient in the Study until the visit time (i.e. the "clinical benefit") a | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The long-term effect of givinostat on each single response parameter according to the revised ELN (For PV and ET) and EUMNET response criteria (for MF) • Long-term reduction of the JAK2 v617F allele burden by quantitative RT-PCR • Identification of potential other markers predictive of clinical benefit of givinostat (e.g. potential PD markers). Evaluation of the parameters that allows to evaluate the disease evolution and history (e.g. thrombotic rate, PFC etc.) ;Timepoint(s) of evaluation of this end point: The secondary endpoint will be assessed at each quarterly visit. | — |
Countries
Germany, Italy, Poland
Contacts
Public ContactClinical Research&Development Dept
Italfarmaco S.p.A.
Outcome results
None listed