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

NCT ID: NCT06093672

Last Updated: 2026-01-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

220 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-03-26

Study Completion Date

2026-07-31

Brief Summary

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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

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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.

Conditions

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Polycythemia Vera

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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Givinostat - Core phase

Givinostat 50 mg BID from baseline till week 48

Group Type EXPERIMENTAL

Givinostat

Intervention Type DRUG

Oral. The dosage must be modified, according to the manifestation of toxicities or lack of efficacy, with the aim to achieve an optimized dose.

Hydroxyurea - Core phase

HU 500 mg BID from baseline till week 48

Group Type ACTIVE_COMPARATOR

Hydroxyurea

Intervention Type DRUG

Oral. The dosage must be modified, according to the manifestation of toxicities or lack of efficacy, with the aim to achieve an optimized dose.

Interventions

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Givinostat

Oral. The dosage must be modified, according to the manifestation of toxicities or lack of efficacy, with the aim to achieve an optimized dose.

Intervention Type DRUG

Hydroxyurea

Oral. The dosage must be modified, according to the manifestation of toxicities or lack of efficacy, with the aim to achieve an optimized dose.

Intervention Type DRUG

Other Intervention Names

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ITF2357 ITF2357

Eligibility Criteria

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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


* 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

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


* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PPD Development, LP

INDUSTRY

Sponsor Role collaborator

Italfarmaco

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status NOT_YET_RECRUITING

Emad Ibrahim, MD, Inc

Redlands, California, United States

Site Status RECRUITING

US Oncology Inc

Englewood, Colorado, United States

Site Status RECRUITING

American Oncology Partners of Maryland, PA

Bethesda, Maryland, United States

Site Status RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Site Status RECRUITING

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Site Status RECRUITING

Oncology Associates of Oregon, P.C.

Eugene, Oregon, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

Texas Oncology (Webster) - USOR

Houston, Texas, United States

Site Status RECRUITING

Texas Oncology-Denison Cancer Center

Sherman, Texas, United States

Site Status RECRUITING

University of Utah - Huntsman Cancer Institute - PPDS

Salt Lake City, Utah, United States

Site Status RECRUITING

The James Cancer Hospital and Solove Research Institute

Roanoke, Virginia, United States

Site Status RECRUITING

VA Puget Sound Health Care System - NAVREF - PPDS

Seattle, Washington, United States

Site Status RECRUITING

Landesklinikum Wiener Neustadt

Wiener Neustadt, Lower Austria, Austria

Site Status RECRUITING

Ordensklinikum Linz GmbH Elisabethinen

Linz, Upper Austria, Austria

Site Status RECRUITING

Klinikum Wels-Grieskirchen GmbH

Wels, Upper Austria, Austria

Site Status RECRUITING

Medizinische Universitat Wien (Medical University of Vienna)

Vienna, Vienna, Austria

Site Status RECRUITING

Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda

Sofia, Sofia-Grad, Bulgaria

Site Status RECRUITING

University Multiprofile Hospital for Active Treatment Sveti Georgi EAD

Plovdiv, , Bulgaria

Site Status RECRUITING

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

Stara Zagora, , Bulgaria

Site Status RECRUITING

Clinical Hospital Dubrava

Zagreb, City of Zagreb, Croatia

Site Status RECRUITING

Clinical Hospital Center Rijeka - PPDS

Rijeka, , Croatia

Site Status RECRUITING

Clinical Hospital Center Rijeka

Rijeka, , Croatia

Site Status NOT_YET_RECRUITING

General Hospital Sibenik

Šibenik, , Croatia

Site Status NOT_YET_RECRUITING

Centre Hospitalier de Saint-Quentin

Saint-Quentin, Aisne, France

Site Status RECRUITING

CHU de Nice

Nice, Alpes-Maritimes, France

Site Status RECRUITING

Centre Hospitalier de Troyes

Troyes, Aube, France

Site Status RECRUITING

Hôpital Bretonneau

Tours, Indre-et-Loire, France

Site Status RECRUITING

CHU Nantes

Nantes, Loire-Atlantique, France

Site Status RECRUITING

CHU Angers

Angers, Maine-et-Loire, France

Site Status RECRUITING

CHU Amiens Hôpital Sud

Amiens, Somme, France

Site Status RECRUITING

Hôpital Saint Louis

Paris, , France

Site Status RECRUITING

Hopital d'Argenteuil

Argenteuil, Île-de-France Region, France

Site Status NOT_YET_RECRUITING

Medizinische Fakultät Mannheim der Universität Heidelberg, Universitätsmedizin Mannheim

Mannheim, Baden-Wurttemberg, Germany

Site Status RECRUITING

Gemeinschaftspraxis Hämatologie - Onkologie

Dresden, Saxony, Germany

Site Status RECRUITING

Universitätsmedizin Halle, Universitätsklinikum Halle, Klinik für Innere Medizin IV

Halle, Saxony-Anhalt, Germany

Site Status RECRUITING

OncoResearch Lerchenfeld GmbH

Hamburg, , Germany

Site Status RECRUITING

Gyor-Moson-Sopron Vármegyei Petz Aladár Egyetemi Oktató Kórház

Győr, Győr-Moson-Sopron, Hungary

Site Status RECRUITING

Szabolcs-Szatmár-Bereg Vármegyei Oktatókórház

Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

Site Status RECRUITING

Tolna Vármegyei Megyei Balassa János Kórház

Szekszárd, Tolna County, Hungary

Site Status RECRUITING

Cork University Hospital

Cork, , Ireland

Site Status RECRUITING

Connolly Hospital Blanchardstown

Dublin, , Ireland

Site Status NOT_YET_RECRUITING

Mater Misericordiae University Hospital

Dublin, , Ireland

Site Status RECRUITING

Hadassah Medical Center - PPDS

Jerusalem, Jerusalem, Israel

Site Status TERMINATED

Assuta Medical Center

Tel Aviv, Tel Aviv, Israel

Site Status RECRUITING

Bnai Zion Medical Center

Haifa, , Israel

Site Status TERMINATED

Carmel Medical Center

Haifa, , Israel

Site Status TERMINATED

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

Bari, Apulia, Italy

Site Status RECRUITING

Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli

Reggio Calabria, Calabria, Italy

Site Status RECRUITING

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

Bologna, Emilia-Romagna, Italy

Site Status RECRUITING

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

Meldola, Emilia-Romagna, Italy

Site Status RECRUITING

Azienda USL IRCCS di Reggio Emilia

Reggio Emilia, Emilia-Romagna, Italy

Site Status RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale

Udine, Friuli Venezia Giulia, Italy

Site Status RECRUITING

Fondazione Policlinico Universitario Campus Bio-Medico di Roma

Rome, Lazio, Italy

Site Status RECRUITING

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, Lombardy, Italy

Site Status RECRUITING

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Lombardy, Italy

Site Status RECRUITING

Azienda Sanitaria Ospedaliera S. Croce e Carle

Cuneo, Piedmont, Italy

Site Status RECRUITING

A.O.U. Maggiore della Carità

Novara, Piedmont, Italy

Site Status RECRUITING

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, Piedmont, Italy

Site Status RECRUITING

Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco di Catania

Catania, Sicily, Italy

Site Status NOT_YET_RECRUITING

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, Sicily, Italy

Site Status RECRUITING

Azienda Ospedaliero Universitaria delle Marche

Ancona, The Marches, Italy

Site Status RECRUITING

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, Italy

Site Status RECRUITING

Spaarne Gasthuis

Hoofddorp, North Holland, Netherlands

Site Status NOT_YET_RECRUITING

Medisch Spectrum Twente

Enschede, Overijssel, Netherlands

Site Status NOT_YET_RECRUITING

Albert Schweitzer Ziekenhuis

Dordrecht, South Holland, Netherlands

Site Status NOT_YET_RECRUITING

Indywidualna Specjalistyczna Praktyka Lekarska Tomasz Woźny

Poznan, , Poland

Site Status RECRUITING

Specjalistyczny Szpital im. dra Alfreda Sokołowskiego

Wałbrzych, , Poland

Site Status RECRUITING

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza- Radeckiego we Wrocławiu

Wroclaw, , Poland

Site Status NOT_YET_RECRUITING

Clinical Hospital Center Bezanijska Kosa

Belgrade, , Serbia

Site Status RECRUITING

Clinical Hospital Center Zemun

Belgrade, , Serbia

Site Status RECRUITING

University Clinical Center of Serbia

Belgrade, , Serbia

Site Status RECRUITING

University Clinical Center Nis

Niš, , Serbia

Site Status RECRUITING

Clinical Center of Vojvodina

Novi Sad, , Serbia

Site Status RECRUITING

ICO Badalona-H.U. Germans Trias i Pujol

Badalona, Barcelona, Spain

Site Status NOT_YET_RECRUITING

Hospital General Universitario Dr. Balmis

Alicante, , Spain

Site Status RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, , Spain

Site Status RECRUITING

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, , Spain

Site Status RECRUITING

Belfast City Hospital

Belfast, , United Kingdom

Site Status NOT_YET_RECRUITING

Imperial College Healthcare NHS Trust

London, , United Kingdom

Site Status RECRUITING

Countries

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United States Austria Bulgaria Croatia France Germany Hungary Ireland Israel Italy Netherlands Poland Serbia Spain United Kingdom

Central Contacts

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Maurizio Caserini

Role: CONTACT

+39 02 6443 1

Facility Contacts

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Victor Priego

Role: primary

Other Identifiers

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DSC/08/2357/32

Identifier Type: -

Identifier Source: org_study_id

2022-502276-23-00

Identifier Type: CTIS

Identifier Source: secondary_id

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