A two-part study to investigate the safety and preliminary efficacy of Givinostat in patients with Polycythemia Vera

Phase 1

• Conditions: JAK2V617F positive Polycythemia Vera; MedDRA version: 14.1Level: LLTClassification code 10036061Term: Polycythemia veraSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2013-000860-27-IT
• Lead Sponsor: ITALFARMACO S.p.A

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2013-04-18
• Last Update Posted: 27 August 2018

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 52

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 <45% in need of phlebotomy, and
b)PLT counts > 400 x109/L, and
c)WBC > 10 x109/L;

Note that if the enrolment in Part A is slow (i.e. < 5 patients enrolled in 3 months), eligibility for this part of the study may be expanded to all patients with cMPN. In this case, the inclusion criteria 5 will be modified as following only for Part A:
5. Patients must have an active/not controlled disease defined as:
a)ET patients: PLT counts > 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

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 < 100 x109/L within 14 days before enrolment (i.e. the receipt of the Patient ID);

9.Absolute neutrophil count < 1.2x109/L within 14 days before enrolment (i.e. the receipt of the Patient ID);

10.Serum creatinine > 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.

Study & Design

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