Study on Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera

Phase 3

Recruiting

• Conditions: Polycythemia Vera
• Interventions: Drug: Hydroxyurea; Drug: Givinostat

• Registration Number: NCT06093672
• Lead Sponsor: Italfarmaco

Brief Summary

The goal of this clinical trial is to compare the efficacy and safety of givinostat to hydroxyurea in Jak2V617F-positive high risk polycythemia vera patients.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-10-10
• Study First Submitted QC: 2023-10-19
• Study First Posted: 2023-10-23
• Study Start: 2024-03-26
• Status Verified: 2024-07
• Last Update Submitted: 2024-12-05
• Last Update Posted: 2024-12-06
• Primary Completion: 2026-07
• Study Completion: 2026-07

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

• Patients must have been diagnosed with PV according to the 2016 WHO criteria within 3 years before randomization

• Patients must have JAK2V617F-positive disease

• Patients with PV must meet the definition of HR for thrombosis (i.e., HR) at screening as follows:

  • Age ≥ 60 years, and/or
  • Prior thrombosis.

• Patients must be in need of treatment at screening, defined by the presence of at least one of the following:

  • HCT ≥ 45% or HCT < 45% with at least 1 phlebotomy performed in the 3 months before screening, or
  • WBC count > 10 × 109/L, or
  • PLT count > 400 × 109/L.

• Patients must have normalized HCT (i.e., HCT < 45%) at randomization

Exclusion Criteria

• Patients pre-treated with HU with a documented history of resistance or intolerance to HU defined by the original ELN criteria
• Patients with a QTcF value of > 450 msec for males and > 460 msec for females at the Screening visit (as the mean of 3 consecutive readings 5 minutes apart in the event a first ECG demonstrates a prolonged QTcF interval); congenital or acquired history of QTc prolongation or ventricular arrhythmias, at the Screening visit
• Splanchnic thrombosis and/or thrombosis of the cerebral venous sinuses and/or splenectomy in the medical history
• Patients with clinically significant cardiovascular disease
• Patients with myocardial infarction, stroke or unstable angina within the 6 months prior to screening.
• Patients with inadequate liver or renal function at screening
• Uncontrolled hypertriglyceridemia at screening, i.e., triglycerides ˃ 1.5 × ULN
• Previous treatment with a JAK2 or HDAC inhibitor or 32-phosphorus (radioactive isotope) therapy.
• Patients being treated concurrently with any investigational agent or prior participation in an interventional clinical study within the 30 days prior to screening or within 5 half-lives of the investigational product, whichever is longer.
• Pregnant or nursing women

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Hydroxyurea	Hydroxyurea	-
Givinostat	Givinostat	-

Primary Outcome Measures

Name	Time	Method
Proportion of patients achieving a response at Week 48.	week 25 - week 48	Response assessment based on: * Hematocrit \< 45% without phlebotomy in the prior 3 months, and; * White blood cell (WBC) count ≤ 10 × 109/L, and; * Platelet count ≤ 400 × 109/L, and; * Normal spleen size as measured by imaging (normal spleen size is defined as: a longitudinal diameter ≤ 12 cm for female and ≤ 13 cm for male) and; * During Part 2 (Week 25 to 48), absence of progressive disease, major hemorrhagic events and major thrombotic events.

Secondary Outcome Measures

Name	Time	Method
Proportion of patients achieving a complete hematological response (CHR) at Week 48.	week 48	CHR based on: * Hematocrit \< 45% without phlebotomy in the prior 3 months, and; * White blood cell (WBC) count ≤ 10 × 109/L, and; * Platelet count ≤ 400 × 109/L
Safety and tolerability up to Week 48.	Randomization - week 48
Time from randomization to the first observed CHR	Randomization - week 48
Proportion of patients with a normal spleen size at Week 48.	week 48

Trial Locations

Locations (76)

VA Puget Sound Health Care System - NAVREF - PPDS; 🇺🇸 Seattle, Washington, United States

The Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Hopital d'Argenteuil; 🇫🇷 Argenteuil, Île-de-France, France

CHU Angers; 🇫🇷 Angers, Maine-et-Loire, France

Clinical Hospital Center Zagreb; 🇭🇷 Zagreb, Grad Zagreb, Croatia

Clinical Hospital Dubrava; 🇭🇷 Zagreb, Grad Zagreb, Croatia

CHU de Nice; 🇫🇷 Nice, Alpes-Maritimes, France

Gyor-Moson-Sopron Vármegyei Petz Aladár Egyetemi Oktató Kórház; 🇭🇺 Győr, Győr-Moson-Sopron, Hungary

Connolly Hospital Blanchardstown; 🇮🇪 Dublin, Ireland

Mater Misericordiae University Hospital; 🇮🇪 Dublin, Ireland

Assuta Medical Center; 🇮🇱 Tel Aviv-Yafo, Tel-Aviv, Israel

Hadassah Medical Center - PPDS; 🇮🇱 Jerusalem, Yerushalayim, Israel

Bnai Zion Medical Center; 🇮🇱 Haifa, Israel

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza- Radeckiego we Wrocławiu; 🇵🇱 Wrocław, Poland

ICO Badalona-H.U. Germans Trias i Pujol; 🇪🇸 Badalona, Barcelona, Spain

Medisch Spectrum Twente; 🇳🇱 Enschede, Overijssel, Netherlands

Azienda Ospedaliero Universitaria delle Marche; 🇮🇹 Ancona, Marche, Italy

Carmel Medical Center; 🇮🇱 Haifa, Israel

Fondazione Policlinico Universitario Campus Bio-Medico di Roma; 🇮🇹 Roma, Lazio, Italy

University Multiprofile Hospital for Active Treatment Sveti Georgi EAD; 🇧🇬 Plovdiv, Bulgaria

CHU Nantes; 🇫🇷 Nantes, Loire-Atlantique, France

Szabolcs-Szatmár-Bereg Vármegyei Oktatókórház; 🇭🇺 Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

Cork University Hospital; 🇮🇪 Cork, Ireland

Spaarne Gasthuis; 🇳🇱 Hoofddorp, Noord-Holland, Netherlands

Albert Schweitzer Ziekenhuis; 🇳🇱 Dordrecht, Zuid-Holland, Netherlands

Clinical Hospital Center Zemun; 🇷🇸 Belgrade, Serbia

Hôpital Bretonneau; 🇫🇷 Tours, Indre-et-Loire, France

Medizinische Fakultät Mannheim der Universität Heidelberg, Universitätsmedizin Mannheim; 🇩🇪 Mannheim, Baden-Württemberg, Germany

Landesklinikum Wiener Neustadt; 🇦🇹 Wiener Neustadt, Niederösterreich, Austria

Ordensklinikum Linz GmbH Elisabethinen; 🇦🇹 Linz, Oberösterreich, Austria

Klinikum Wels-Grieskirchen GmbH; 🇦🇹 Wels, Oberösterreich, Austria

Centre Hospitalier de Saint-Quentin; 🇫🇷 Saint-Quentin, Aisne, France

CHU Amiens Hôpital Sud; 🇫🇷 Amiens, Somme, France

Fejer Varmegyei Szent Gyorgy Egyetemi Oktato Korhaz; 🇭🇺 Székesfehérvár, Fejer, Hungary

University Clinical Center of Serbia; 🇷🇸 Belgrade, Serbia

Medizinische Universitat Wien (Medical University of Vienna); 🇦🇹 Vienna, Wien, Austria

Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda; 🇧🇬 Sofia, Sofia-Grad, Bulgaria

University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich AD; 🇧🇬 Stara Zagora, Bulgaria

Centre Hospitalier de Troyes; 🇫🇷 Troyes, Aube, France

Indywidualna Specjalistyczna Praktyka Lekarska Tomasz Woźny; 🇵🇱 Poznań, Poland

Clinical Center of Vojvodina; 🇷🇸 Novi Sad, Serbia

Azienda Ospedaliera Papa Giovanni XXIII; 🇮🇹 Bergamo, Lombardia, Italy

A.O.U. Maggiore della Carità; 🇮🇹 Novara, Piemonte, Italy

Istituto Tumori "Giovanni Paolo II" I.R.C.C.S.; 🇮🇹 Bari, Puglia, Italy

Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco di Catania; 🇮🇹 Catania, Sicilia, Italy

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone; 🇮🇹 Palermo, Sicilia, Italy

University of Alabama at Birmingham; 🇺🇸 Birmingham, Alabama, United States

University of Utah - Huntsman Cancer Institute - PPDS; 🇺🇸 Salt Lake City, Utah, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Clinical Hospital Center Rijeka; 🇭🇷 Rijeka, Croatia

General Hospital Sibenik; 🇭🇷 Šibenik, Croatia

Hôpital Saint Louis; 🇫🇷 Paris, France

Universitätsmedizin Halle, Universitätsklinikum Halle, Klinik für Innere Medizin IV; 🇩🇪 Halle (Saale), Sachsen-Anhalt, Germany

Gemeinschaftspraxis Hämatologie - Onkologie; 🇩🇪 Dresden, Sachsen, Germany

Tolna Vármegyei Megyei Balassa János Kórház; 🇭🇺 Szekszárd, Tolna, Hungary

Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli; 🇮🇹 Reggio Calabria, Calabria, Italy

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico; 🇮🇹 Bologna, Emilia-Romagna, Italy

Azienda Sanitaria Universitaria Friuli Centrale; 🇮🇹 Udine, Friuli-Venezia Giulia, Italy

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l; 🇮🇹 Meldola, Emilia-Romagna, Italy

Azienda USL IRCCS di Reggio Emilia; 🇮🇹 Reggio Emilia, Emilia-Romagna, Italy

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico; 🇮🇹 Milano, Lombardia, Italy

Azienda Sanitaria Ospedaliera S. Croce e Carle; 🇮🇹 Cuneo, Piemonte, Italy

Azienda Ospedaliera Città della Salute e della Scienza di Torino; 🇮🇹 Torino, Piemonte, Italy

Azienda Ospedaliera Universitaria Careggi; 🇮🇹 Firenze, Toscana, Italy

Specjalistyczny Szpital im. dra Alfreda Sokołowskiego; 🇵🇱 Wałbrzych, Poland

Clinical Hospital Center Bezanijska Kosa; 🇷🇸 Belgrade, Serbia

University Clinical Center Nis; 🇷🇸 Nis, Serbia

Hospital General Universitario Dr. Balmis; 🇪🇸 Alicante, Spain

Hospital Universitari i Politecnic La Fe de Valencia; 🇪🇸 Valencia, Spain

Hospital Universitario Virgen de la Victoria; 🇪🇸 Málaga, Spain

Imperial College Healthcare NHS Trust; 🇬🇧 London, United Kingdom

Belfast City Hospital; 🇬🇧 Belfast, United Kingdom

OncoResearch Lerchenfeld GmbH; 🇩🇪 Hamburg, Germany

Hospital Universitario Ramon y Cajal; 🇪🇸 Madrid, Spain

Emad Ibrahim, MD, Inc; 🇺🇸 Redlands, California, United States