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NCT06093672PHASE3Recruiting

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

Italfarmaco

Start Date

3/26/2024

Completion Date

7/1/2026

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

PV is a cMPN mainly driven by JAK2V617F mutation. The disease has an increased risk of thromboembolic complications, a predisposition to evolve into myelofibrosis (MF) and transformation into acute myeloid leukemia. Patients ≥ 60 years of age and/or with a previous thrombotic event (TE) are considered at High Risk (HR) for thrombosis. The association of absolute values of circulating neutrophil, lymphocyte and monocyte and the high value of JAK2V617F allele burden are additional risk factors for the occurrence of thrombosis and for progression to MF, respectively. Overall, most patients treated with HU are not adequately under control for both symptoms and long-term risks. In recent years, data have shown that histone deacetylase (HDACs) inhibitors induce growth arrest, differentiation, and/or apoptosis in neoplastic cells. Givinostat has demonstrated preliminary signs of clinical activity and an acceptable safety profile in patients with JAK2V617F-positive cMPNs in three phase 2 studies. The core treatment phase (pivotal phase 3 study) is designed to demonstrate the superiority of givinostat versus HU on efficacy, in JAK2V617F-positive, HR PV patients. The extended treatment phase will allow eligible patients to receive givinostat in the long-term, with the objective of collecting long-term safety and efficacy data.

Eligibility Criteria

Age Range: 18 years to No maximum

Core Treatment - Inclusion Criteria: * Patients must have been diagnosed with PV according to the 2016 WHO criteria before randomization * Patients must have JAK2V617F-positive disease * Patients with PV must meet the definition of HR for thrombosis (i.e., HR) within 3 years before 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 Extended Treatment - Inclusion Criteria * Patients must have completed the Week 48 visit of the DSC/08/2357/32 core treatment phase and: 1. if the patient received givinostat, a complete hematological response (CHR) at Week 48 shall be achieved 2. if the patient received HU, did not achieve a CHR (see above for the definition) at Week 48 Core Treatment phase - 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 Extended treatment phase - Exclusion criteria * For patients randomized to givinostat in the core treatment phase - Patients with a QTcF value at Week 48 of \> 500 msec * For patients randomized to HU in the core treatment phase: * PLT count ≤ 150 × 109/L at Week 48 * ANC \< 1.2 × 109/L at Week 48 * Uncontrolled hypertriglyceridemia at Week 48 * Patients with a QTcF value at Week 48 of \> 450 msec for males and \> 460 msec for female

Interventions

DRUG

Givinostat

DRUG

Hydroxyurea

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Conditions

Polycythemia Vera

Locations

University of Alabama at Birmingham

Birmingham, Alabama 35294-0001

United States

Emad Ibrahim, MD, Inc

Redlands, California 92373

United States

US Oncology Inc

Englewood, Colorado 80113

United States

American Oncology Partners of Maryland, PA

Bethesda, Maryland 20852

United States

Icahn School of Medicine at Mount Sinai

New York, New York 10029

United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina 27599

United States

The Cleveland Clinic Foundation

Cleveland, Ohio 44195

United States

Oncology Associates of Oregon, P.C.

Eugene, Oregon 97401

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

Texas Oncology (Webster) - USOR

Houston, Texas 77089

United States

Texas Oncology-Denison Cancer Center

Sherman, Texas 75090

United States

University of Utah - Huntsman Cancer Institute - PPDS

Salt Lake City, Utah 84112

United States

The James Cancer Hospital and Solove Research Institute

Roanoke, Virginia 43210

United States

VA Puget Sound Health Care System - NAVREF - PPDS

Seattle, Washington 98108-1532

United States

Landesklinikum Wiener Neustadt

Wiener Neustadt, Lower Austria 2700

Austria

Medizinische Universitat Wien (Medical University of Vienna)

Vienna, State of Vienna 1090

Austria

Ordensklinikum Linz GmbH Elisabethinen

Linz, Upper Austria 4020

Austria

Klinikum Wels-Grieskirchen GmbH

Wels, Upper Austria 4600

Austria

Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda

Sofia, Sofia-Grad 1407

Bulgaria

University Multiprofile Hospital for Active Treatment Sveti Georgi EAD

Plovdiv, 4001

Bulgaria

University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich AD

Stara Zagora, 6003

Bulgaria

Clinical Hospital Dubrava

Zagreb, City of Zagreb 10000

Croatia

Clinical Hospital Center Rijeka - PPDS

Rijeka, 51000

Croatia

Clinical Hospital Center Rijeka

Rijeka, 51000

Croatia

General Hospital Sibenik

Šibenik, 22000

Croatia

Centre Hospitalier de Saint-Quentin

Saint-Quentin, Aisne 2100

France

CHU de Nice

Nice, Alpes-Maritimes 6202

France

Centre Hospitalier de Troyes

Troyes, Aube 10000

France

Hôpital Bretonneau

Tours, Indre-et-Loire 37044

France

CHU Nantes

Nantes, Loire-Atlantique 44000

France

CHU Angers

Angers, Maine-et-Loire 49000

France

CHU Amiens Hôpital Sud

Amiens, Somme 80054

France

Hôpital Saint Louis

Paris, 75010

France

Hopital d'Argenteuil

Argenteuil, Île-de-France Region 95107

France

Medizinische Fakultät Mannheim der Universität Heidelberg, Universitätsmedizin Mannheim

Mannheim, Baden-Wurttemberg 68167

Germany

Gemeinschaftspraxis Hämatologie - Onkologie

Dresden, Saxony 01307

Germany

Universitätsmedizin Halle, Universitätsklinikum Halle, Klinik für Innere Medizin IV

Halle, Saxony-Anhalt 06120

Germany

OncoResearch Lerchenfeld GmbH

Hamburg, 22081

Germany

Gyor-Moson-Sopron Vármegyei Petz Aladár Egyetemi Oktató Kórház

Győr, Győr-Moson-Sopron 9024

Hungary

Szabolcs-Szatmár-Bereg Vármegyei Oktatókórház

Nyíregyháza, Szabolcs-Szatmár-Bereg 4400

Hungary

Tolna Vármegyei Megyei Balassa János Kórház

Szekszárd, Tolna County 7100

Hungary

Cork University Hospital

Cork,

Ireland

Connolly Hospital Blanchardstown

Dublin, 15

Ireland

Mater Misericordiae University Hospital

Dublin, 7

Ireland

Hadassah Medical Center - PPDS

Jerusalem, Jerusalem 91120

Israel

Assuta Medical Center

Tel Aviv, Tel Aviv 60000

Israel

Bnai Zion Medical Center

Haifa, 31048

Israel

Carmel Medical Center

Haifa, 34362

Israel

Istituto Tumori "Giovanni Paolo II" I.R.C.C.S.

Bari, Apulia 70124

Italy

Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli

Reggio Calabria, Calabria 89133

Italy

Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico

Bologna, Emilia-Romagna 40138

Italy

Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l

Meldola, Emilia-Romagna 47014

Italy

Azienda USL IRCCS di Reggio Emilia

Reggio Emilia, Emilia-Romagna 42123

Italy

Azienda Sanitaria Universitaria Friuli Centrale

Udine, Friuli Venezia Giulia 33100

Italy

Fondazione Policlinico Universitario Campus Bio-Medico di Roma

Rome, Lazio 00128

Italy

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, Lombardy 24127

Italy

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Lombardy 20122

Italy

Azienda Sanitaria Ospedaliera S. Croce e Carle

Cuneo, Piedmont 12100

Italy

A.O.U. Maggiore della Carità

Novara, Piedmont 28100

Italy

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, Piedmont 10126

Italy

Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco di Catania

Catania, Sicily 95123

Italy

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, Sicily 90127

Italy

Azienda Ospedaliero Universitaria delle Marche

Ancona, The Marches 60126

Italy

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany 50134

Italy

Spaarne Gasthuis

Hoofddorp, North Holland 2134 TM

Netherlands

Medisch Spectrum Twente

Enschede, Overijssel 7512 KZ

Netherlands

Albert Schweitzer Ziekenhuis

Dordrecht, South Holland 3318 AT

Netherlands

Indywidualna Specjalistyczna Praktyka Lekarska Tomasz Woźny

Poznan, 60-549

Poland

Specjalistyczny Szpital im. dra Alfreda Sokołowskiego

Wałbrzych, 58-309

Poland

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza- Radeckiego we Wrocławiu

Wroclaw, 50-367

Poland

Clinical Hospital Center Bezanijska Kosa

Belgrade, 11000

Serbia

Clinical Hospital Center Zemun

Belgrade, 11000

Serbia

University Clinical Center of Serbia

Belgrade, 11000

Serbia

University Clinical Center Nis

Niš, 18000

Serbia

Clinical Center of Vojvodina

Novi Sad, 21000

Serbia

ICO Badalona-H.U. Germans Trias i Pujol

Badalona, Barcelona 8916

Spain

Hospital General Universitario Dr. Balmis

Alicante, 3010

Spain

Hospital Universitario Ramon y Cajal

Madrid, 28034

Spain

Hospital Universitario Virgen de la Victoria

Málaga, 29010

Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026

Spain

Medical Park Bahcelievler Hastanesi

Bahçelievler, Istanbul

Turkey (Türkiye)

Ege Universitesi Tip Fakultesi

Bornova, İzmir

Turkey (Türkiye)

VM Medical Park Mersin Hospital - Ataturk

Mezitli, Mersin

Turkey (Türkiye)

Namik Kemal Universitesi Saglik Uygulama ve Arastirma Merkezi

Altınova, Terkirdag

Turkey (Türkiye)

Belfast City Hospital

Belfast, BT9 7AB

United Kingdom

Pilgrim Hospital

Boston,

United Kingdom

Imperial College Healthcare NHS Trust

London, W12 0HS

United Kingdom

Milton Keynes University Hospital

Milton Keynes,

United Kingdom

University of Oxford - The Weatherall Institute of Molecular Medicine (WIMM)

Oxford,

United Kingdom

Southampton General Hospital

Southampton,

United Kingdom