ong-term Study Evaluating the Effect of givinostat in Patients With Chronic Myeloproliferative Neoplasms

Phase 1

• Conditions: Chronic myeloproliferative neoplasm; MedDRA version: 20.0Level: HLTClassification code 10028578Term: Myeloproliferative disorders (excl leukaemias)System Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 20.0Level: SOCClassification code 10005329Term: Blood and lymphatic system disordersSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2012-003499-37-DE
• Lead Sponsor: ITALFARMACO S.p.A

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-12-02
• Last Update Posted: 10 May 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 90

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 <3 at baseline

5. Acceptable organ function within 7 days of initiating study drug

6. 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

7. 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 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

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 <100 x109/L within 14 days before enrolment

7. Absolute neutrophil count < 1.2 x109/L within 14 days before enrolment

8. Total serum bilirubin >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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified