Status:

COMPLETED

A Two-part Study to Assess the Safety and Preliminary Efficacy of Givinostat in Patients With Polycythemia Vera

Lead Sponsor:

Italfarmaco

Conditions:

Polycythemia Vera

Eligibility:

All Genders

18+ years

Phase:

PHASE1

PHASE2

Brief Summary

This is a two-part, multicenter, open label, non-randomized, phase Ib/II study to assess the safety and tolerability, Maximum Tolerated Dose and preliminary efficacy of Givinostat in patients with JAK...

Detailed Description

This is a two-part, multicenter, open label, non-randomized, phase Ib/II study to assess the safety and tolerability, MTD and preliminary efficacy of Givinostat in patients with JAK2V617F positive PV....

Eligibility Criteria

Inclusion

  • Patients must be able to provide informed consent and be willing to sign an informed consent form;
  • Patients must have an age ≥18 years;
  • Patients must have a confirmed diagnosis of Polycythemia Vera according to the revised World Health Organization criteria;
  • Patients must have mutated Janus Kinase 2 (mutation V617F) positive disease;
  • Patients must have an active/not controlled disease defined as
  • hematocrit ≥ 45% or hematocrit \<45% in need of phlebotomy, and
  • platelet count \> 400 x109/L, and
  • white blood cell count \> 10 x109/L;
  • 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;
  • Female patient of childbearing potential has a negative serum or urine pregnancy test within 72 hours of the first dose of study therapy;
  • Use of an effective means of contraception for women of childbearing potential and men with partners of childbearing potential;
  • Adequate and acceptable organ function within 7 days of initiating study drug;
  • Willingness and capability to comply with the requirements of the study.
  • 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 chronic myeloproliferative neoplasms. 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:
  • Essential Thrombocythemia patients: Platelet count \> 600 x109/L;
  • Myelofibrosis patients: no response according to European Myelofibrosis Network criteria.

Exclusion

  • Active bacterial or mycotic infection requiring antimicrobial treatment;
  • Pregnancy or nursing;
  • A clinically significant corrected QT interval prolongation at baseline;
  • Use of concomitant medications known to prolong the corrected QT interval;
  • Clinically significant cardiovascular disease including:
  • Uncontrolled hypertension despite medical treatment, myocardial infarction, unstable angina within 6 months from study start;
  • New York Heart Association 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;
  • Known positivity for human immunodeficiency;
  • Known active hepatitis B virus and/or hepatitis C virus infection;
  • Platelet count \< 100 x109/L within 14 days before enrolment;
  • Absolute neutrophil count \< 1.2x109/L within 14 days before enrolment;
  • Serum creatinine \> 2 times the upper limit of normal;
  • Total serum bilirubin \> 1.5 times the upper limit of normal except in case of Gilbert's disease;
  • Serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) \> 3 times the upper limit of normal;
  • 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;
  • Prior treatment with a Janus Kinase 2 or Histone Deacetylase inhibitor or participation in an interventional clinical trial for chronic myeloproliferative neoplasms;
  • Systemic treatment for chronic myeloproliferative neoplasms other than aspirin/cardio aspirin;
  • Hydroxyurea within 28 days before enrolment;
  • Interferon alpha within 14 days before enrolment;
  • Anagrelide within 7 days before enrolment;
  • Any other investigational drug or device within 28 days before enrolment;
  • Patient with known hypersensitivity to the components of study therapy.

Key Trial Info

Start Date :

October 1 2013

Trial Type :

INTERVENTIONAL

Allocation :

ACTUAL

End Date :

September 25 2017

Estimated Enrollment :

48 Patients enrolled

Trial Details

Trial ID

NCT01901432

Start Date

October 1 2013

End Date

September 25 2017

Last Update

July 30 2019

Active Locations (25)

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Page 1 of 7 (25 locations)

1

CHU Amiens - Hôpital Sud

Amiens, France, 80054

2

Hôpital Morvan - CHRU de Brest

Brest, France, 29609

3

Hopital Saint Vincent de Paul - GHICL Lille

Lille, France, 59020

4

Hôpital Saint-Louis (AP-HP), Centre Investigations Cliniques

Paris, France, 75475