Phase II Study of GIVINOSTAT (ITF2357) in Combination With Hydroxyurea in Polycythemia Vera

• Status: Completed
• Trial end date: 2011-10-01
• Target enrollment: 0
• Participant gender: All

Summary

The primary objective of the study was to evaluate the efficacy of Givinostat in combination with hydroxyurea in patients with JAK2V617F-positive Polycythemia Vera (PV) non-responders to the maximum tolerated dose of hydroxyurea monotherapy.

The secondary objectives of this study were:

• To evaluate the safety and tolerability of Givinostat in combination with hydroxyurea in patients with JAK2V617Fpositive PV non-responders to the maximum tolerated dose of hydroxyurea monotherapy;

• To explore the impact in terms of efficacy and tolerability of Givinostat 50 mg dose escalation in patients not achieving at least a partial response at the time when the primary endpoint was assessed (week 12);

• To evaluate the molecular response (JAK2 mutated allele burden) by quantitative Real Time-Polymerase Chain Reaction (RT-PCR);

• To evaluate the reduction of the fraction of JAK2V617F positive clonogenic progenitors.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Italfarmaco
• Treatments: Givinostat hydrochloride; Histone Deacetylase Inhibitors; Hydroxyurea

Criteria

Inclusion Criteria:

• Written Informed Consent.

• Age ≥18 years.

• Confirmed diagnosis of Polycythemia Vera according to the revised World Health Organization (WHO) criteria.

• JAK2V617F positivity.

• Non-response to the maximum tolerated dose of hydroxyurea monotherapy for at least 3 months.

• ECOG (Eastern Cooperative Oncology Group) performance status <3.

• Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential.

• Willingness and capability to comply with the requirements of the study.

Exclusion Criteria:

• Active bacterial or mycotic infection requiring antimicrobial treatment.

• Pregnancy or lactation.

• A marked baseline prolongation of QT/QTc (corrected) interval (e.g. repeated demonstration of a QTc interval > 450 ms, according to Bazett's correction formula).

• Use of concomitant medications that prolong the QT/QTc interval.

• Clinically significant cardiovascular disease including:

• Uncontrolled hypertension, myocardial infarction, unstable angin, within 6 months from study start;

• New York Heart Association (NYHA) Grade II or greater congestive heart failure;

• History of any cardiac arrhythmia requiring medication (irrespective of its severity);

• A history of additional risk factors for torsade de pointes (TdP) (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).

• Positive blood test for HIV (Human Immunodeficiency Virus)

• Active HBV (Hepatitis B Virus) and/or HCV (Hepatitis C Virus) infection.

• Platelets count <100x109/L within 14 days before enrolment.

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

• Serum creatinine >2xULN (upper limit of normal).

• Total serum bilirubin >1.5xULN.

• Serum aspartate aminotransferase (AST) / alanine aminotransferase (ALT) > 3xULN.

• History of other diseases, 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.

• Interferon alpha within 14 days before enrolment.

• Anagrelide within 7 days before enrolment.

• Any other investigational drug within 28 days before enrolment.