GIVINOSTAT for Chronic myeloproliferative neoplasm

Inclusion criteria

• {"criterion_text":"- Patients must have completed givinostat treatment on at least one core study in cMPN (i.e. Study DSC/07/2357/28, Study DSC/08/2357/38, Study DSC/12/2357/45 and/or any further 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 benefitat the end of core protocols or compassionate use program with givinostat, assessed bythe Investigator according to the revised clinico-haematological ELN response criteria (for PV and ET) and EUMNET response criteria (for MF)"}
• {"criterion_text":"- Patients must be able to provide informed consent and be willing to sign an informed consent form"}
• {"criterion_text":"- Adult patients (age ≥18 years), of both genders, and with established diagnosis of JAK2V617F positive cMPN according to the revised WHO criteria"}
• {"criterion_text":"- Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status <3 at baseline"}
• {"criterion_text":"- Acceptable organ function within 7 days of initiating study drug"}
• {"criterion_text":"- Use of an effective means of contraception from the 28 days before first dose of study drug through 3 months after the last dose of study drug for women of childbearing potential and men with partners of childbearing potential"}
• {"criterion_text":"- Willingness and capability to comply with the requirements of the study"}

Exclusion criteria

• {"criterion_text":"- 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) and until the termination of gestation"}
• {"criterion_text":"- Uncontrolled hypertriglyceridemia at baseline, i.e. triglycerides >1.5xULN in fasting state."}
• {"criterion_text":"- 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 migh render the patient at high risk from treatment complications or significantly alter the absorption of the study drug"}
• {"criterion_text":"- Any investigational drug other than givinostat within 28 days before enrolment.Notably, the use of such medications within 28 days or 6 halflives - 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"}
• {"criterion_text":"- Patients with known hypersensitivity to the components of potential study therapy"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Clinically significant cardiovascular disease including: • Uncontrolled hypertension, myocardial infarction, unstable angina at screening • 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)"}
• {"criterion_text":"- Active virus infection including HIV, HBV and HCV"}
• {"criterion_text":"- Platelets count <100 x109/L within 14 days before enrolment"}
• {"criterion_text":"- Absolute neutrophil count < 1.2 x109/L within 14 days before enrolment"}
• {"criterion_text":"- Total serum bilirubin >1.5xULN except in case of Gilbert's disease or pattern consistent with Gilbert's disease"}
• {"criterion_text":"- Serum aspartate aminotransferase/alanine aminotransferase AST/ALT >3xULN"}
• {"criterion_text":"- 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)"}

Primary endpoints

• {"endpoint_text":"- Long term safety and tolerability • Number of patients experience adverse events • Type, incidence, and severity of treatment-related adverse events, graded according to the latest available version of Common Terminology Criteria for Adverse Events (CTCAE).","definition_or_measurement_approach":"Assessment by recording number of patients experiencing adverse events; categorisation of type, incidence and severity of treatment-related adverse events graded per latest CTCAE."}
• {"endpoint_text":"- 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. Please refer to the protocol for the full details","definition_or_measurement_approach":"Response rates for PV and ET evaluated by revised clinico-haematological ELN response criteria; MF responses evaluated by EUMNET response criteria (definitions per protocol)."}

Secondary endpoints

• {"endpoint_text":"- The effect of givinostat on each single response parameter according to the revised ELN (For PV and ET) and EUMNET response criteria (for MF)","definition_or_measurement_approach":"Evaluation of individual response parameters per revised ELN and EUMNET criteria."}
• {"endpoint_text":"- Reduction of the JAK2v617F allele burden by quantitative RT-PCR","definition_or_measurement_approach":"Quantitative RT-PCR measurement of JAK2V617F allele burden."}
• {"endpoint_text":"- Identification of potential other markers predictive of clinical benefit of givinostat (e.g. potential PD markers).","definition_or_measurement_approach":"Exploratory biomarker analyses (potential PD markers) as per protocol."}
• {"endpoint_text":"- Evaluation of the parameters that allows to evaluate the disease evolution and history (e.g. thrombotic rate, PFS etc.).","definition_or_measurement_approach":"Assessment of disease evolution parameters including thrombotic rate and progression-free survival (PFS) according to protocol definitions."}

Italy

Earliest CTIS Part Ii Submission Date

10-05-2024

Latest Decision Or Authorization Date

05-12-2025

Processing Time Days

574

Number Of Sites

11

Number Of Participants

48

Primary sponsor

Full Name

Italfarmaco S.p.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Italy

Contract research organisations

Name

IQVIA Limited

Responsibilities

Codes: 1,10,12,2,5,9

Name

Q Squared Solutions Limited

Responsibilities

Cystatin C exams

Name

Mediolanum Cardio Research S.r.l.

Responsibilities

Codes: 6,7

Third parties

• {"country":"United Kingdom","full_name":"Q Squared Solutions Limited","duties_or_roles":"Cystatin C exams","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Italy","full_name":"Careggi University Hospital","duties_or_roles":"Analysis of JAK2V617F gene mutation and molecular markers predictive of clinical benefit","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Codes: 1,10,12,2,5,9","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Pharma Quality Europe S.r.l.","duties_or_roles":"LL & DSUR distribution; code: 8","organisation_type":"Pharmaceutical company"}
• {"country":"Italy","full_name":"Mediolanum Cardio Research S.r.l.","duties_or_roles":"Codes: 6,7","organisation_type":"Pharmaceutical company"}