Study on Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera (GIV-IN-PV)

March 24, 2026 updated by: Italfarmaco

Randomized, Open-label, Multicenter Phase 3 Study to Assess the Efficacy and Safety of GIVinostat Versus Hydroxyurea IN JAK2V617F-positive High-risk Polycythemia Vera Patients: the GIV-IN PV TRIAL

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

220

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Austria
    • Lower Austria
      • Wiener Neustadt, Lower Austria, Austria, 2700
        • Recruiting
        • Landesklinikum Wiener Neustadt
    • Upper Austria
      • Linz, Upper Austria, Austria, 4020
        • Recruiting
        • Ordensklinikum Linz Gmbh Elisabethinen
      • Wels, Upper Austria, Austria, 4600
        • Recruiting
        • Klinikum Wels-Grieskirchen GmbH
    • Vienna
      • Vienna, Vienna, Austria, 1090
        • Recruiting
        • Medizinische Universität Wien (Medical University of Vienna)
  • Bulgaria
      • Plovdiv, Bulgaria, 4001
        • Recruiting
        • University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
      • Stara Zagora, Bulgaria, 6003
        • Recruiting
        • University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich AD
    • Sofia-Grad
      • Sofia, Sofia-Grad, Bulgaria, 1407
        • Recruiting
        • Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda
  • Croatia
      • Rijeka, Croatia, 51000
        • Recruiting
        • Clinical Hospital Center Rijeka - PPDS
      • Rijeka, Croatia, 51000
        • Not yet recruiting
        • Clinical Hospital Center Rijeka
      • Šibenik, Croatia, 22000
        • Not yet recruiting
        • General Hospital Sibenik
    • City of Zagreb
      • Zagreb, City of Zagreb, Croatia, 10000
        • Recruiting
        • Clinical Hospital Dubrava
  • France
      • Paris, France, 75010
        • Recruiting
        • Hopital Saint Louis
    • Aisne
      • Saint-Quentin, Aisne, France, 2100
        • Recruiting
        • Centre Hospitalier de Saint-Quentin
    • Alpes-Maritimes
      • Nice, Alpes-Maritimes, France, 6202
        • Recruiting
        • CHU de Nice
    • Aube
      • Troyes, Aube, France, 10000
        • Recruiting
        • Centre Hospitalier de Troyes
    • Indre-et-Loire
      • Tours, Indre-et-Loire, France, 37044
        • Recruiting
        • Hopital Bretonneau
    • Loire-Atlantique
      • Nantes, Loire-Atlantique, France, 44000
        • Recruiting
        • CHU Nantes
    • Maine-et-Loire
      • Angers, Maine-et-Loire, France, 49000
        • Recruiting
        • CHU Angers
    • Somme
      • Amiens, Somme, France, 80054
        • Recruiting
        • CHU Amiens Hopital SUD
    • Île-de-France Region
      • Argenteuil, Île-de-France Region, France, 95107
        • Recruiting
        • Hopital d'Argenteuil
  • Germany
      • Hamburg, Germany, 22081
        • Recruiting
        • OncoResearch Lerchenfeld GmbH
    • Baden-Wurttemberg
      • Mannheim, Baden-Wurttemberg, Germany, 68167
        • Recruiting
        • Medizinische Fakultät Mannheim der Universität Heidelberg, Universitätsmedizin Mannheim
    • Saxony
      • Dresden, Saxony, Germany, 01307
        • Recruiting
        • Gemeinschaftspraxis Hämatologie - Onkologie
    • Saxony-Anhalt
      • Halle, Saxony-Anhalt, Germany, 06120
        • Withdrawn
        • Universitätsmedizin Halle, Universitätsklinikum Halle, Klinik für Innere Medizin IV
  • Hungary
    • Győr-Moson-Sopron
      • Győr, Győr-Moson-Sopron, Hungary, 9024
        • Recruiting
        • Gyor-Moson-Sopron Varmegyei Petz Aladar Egyetemi Oktato Korhaz
    • Szabolcs-Szatmár-Bereg
      • Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary, 4400
        • Recruiting
        • Szabolcs-Szatmar-Bereg Varmegyei Oktatokorhaz
    • Tolna County
      • Szekszárd, Tolna County, Hungary, 7100
        • Recruiting
        • Tolna Vármegyei Megyei Balassa János Kórház
  • Ireland
      • Cork, Ireland
        • Recruiting
        • Cork University Hospital
      • Dublin, Ireland, 7
        • Recruiting
        • Mater Misericordiae University Hospital
      • Dublin, Ireland, 15
        • Withdrawn
        • Connolly Hospital Blanchardstown
  • Israel
      • Haifa, Israel, 31048
        • Terminated
        • Bnai Zion Medical Center
      • Haifa, Israel, 34362
        • Terminated
        • Carmel Medical Center
    • Jerusalem
      • Jerusalem, Jerusalem, Israel, 91120
        • Terminated
        • Hadassah Medical Center - PPDS
    • Tel Aviv
      • Tel Aviv, Tel Aviv, Israel, 60000
        • Recruiting
        • Assuta Medical Center
  • Italy
    • Apulia
      • Bari, Apulia, Italy, 70124
        • Recruiting
        • Istituto Tumori "Giovanni Paolo II" I.R.C.C.S.
        • Principal Investigator:
          • Paolo Ditonno
    • Calabria
      • Reggio Calabria, Calabria, Italy, 89133
        • Recruiting
        • Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
    • Emilia-Romagna
      • Bologna, Emilia-Romagna, Italy, 40138
        • Recruiting
        • Azienda Ospedaliero-Universitaria di Bologna IRCCS Istituto di Ricerca e di Cura a Carattere Scientifico
      • Meldola, Emilia-Romagna, Italy, 47014
        • Recruiting
        • Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l
      • Reggio Emilia, Emilia-Romagna, Italy, 42123
        • Recruiting
        • Azienda USL IRCCS di Reggio Emilia
    • Friuli Venezia Giulia
      • Udine, Friuli Venezia Giulia, Italy, 33100
        • Recruiting
        • Azienda Sanitaria Universitaria Friuli Centrale
    • Lazio
      • Rome, Lazio, Italy, 00128
        • Recruiting
        • Fondazione Policlinico Universitario Campus Bio-Medico di Roma
    • Lombardy
      • Bergamo, Lombardy, Italy, 24127
        • Recruiting
        • Azienda Ospedaliera Papa Giovanni XXIII
        • Contact:
          • Federico Lussana
      • Milan, Lombardy, Italy, 20122
        • Recruiting
        • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
    • Piedmont
      • Cuneo, Piedmont, Italy, 12100
        • Recruiting
        • Azienda Sanitaria Ospedaliera S. Croce e Carle
      • Novara, Piedmont, Italy, 28100
        • Recruiting
        • A.O.U. Maggiore della Carità
      • Turin, Piedmont, Italy, 10126
        • Recruiting
        • Azienda Ospedaliera Città della Salute e della Scienza di Torino
    • Sicily
      • Catania, Sicily, Italy, 95123
        • Not yet recruiting
        • Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco Di Catania
      • Palermo, Sicily, Italy, 90127
        • Recruiting
        • Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
    • The Marches
      • Ancona, The Marches, Italy, 60126
        • Recruiting
        • Azienda Ospedaliero Universitaria delle Marche
    • Tuscany
      • Florence, Tuscany, Italy, 50134
        • Recruiting
        • Azienda Ospedaliera Universitaria Careggi
  • Netherlands
    • North Holland
      • Hoofddorp, North Holland, Netherlands, 2134 TM
        • Not yet recruiting
        • Spaarne Gasthuis
    • Overijssel
      • Enschede, Overijssel, Netherlands, 7512 KZ
        • Not yet recruiting
        • Medisch Spectrum Twente
    • South Holland
      • Dordrecht, South Holland, Netherlands, 3318 AT
        • Not yet recruiting
        • Albert Schweitzer Ziekenhuis
  • Poland
      • Poznan, Poland, 60-549
        • Recruiting
        • Indywidualna Specjalistyczna Praktyka Lekarska Tomasz Woźny
      • Wałbrzych, Poland, 58-309
        • Recruiting
        • Specjalistyczny Szpital im. dra Alfreda Sokołowskiego
      • Wroclaw, Poland, 50-367
        • Not yet recruiting
        • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza- Radeckiego we Wrocławiu
  • Serbia
      • Belgrade, Serbia, 11000
        • Recruiting
        • Clinical Hospital Center Bezanijska Kosa
      • Belgrade, Serbia, 11000
        • Recruiting
        • Clinical Hospital Center Zemun
      • Belgrade, Serbia, 11000
        • Withdrawn
        • University Clinical Center of Serbia
      • Niš, Serbia, 18000
        • Recruiting
        • University Clinical Center Nis
      • Novi Sad, Serbia, 21000
        • Recruiting
        • Clinical Center of Vojvodina
  • Spain
      • Alicante, Spain, 3010
        • Withdrawn
        • Hospital General Universitario Dr. Balmis
      • Madrid, Spain, 28034
        • Recruiting
        • Hospital Universitario Ramon y Cajal
      • Málaga, Spain, 29010
        • Recruiting
        • Hospital Universitario Virgen de la Victoria
      • Valencia, Spain, 46026
        • Recruiting
        • Hospital Universitari i Politecnic La Fe de Valencia
    • Barcelona
      • Badalona, Barcelona, Spain, 8916
        • Not yet recruiting
        • ICO Badalona-H.U. Germans Trias i Pujol
  • Turkey (Türkiye)
    • Istanbul
      • Bahçelievler, Istanbul, Turkey (Türkiye)
        • Enrolling by invitation
        • Medical Park Bahcelievler Hastanesi
    • Mersin
      • Mezitli, Mersin, Turkey (Türkiye)
        • Recruiting
        • VM Medical Park Mersin Hospital - Ataturk
        • Principal Investigator:
          • ANIL TOMBAK
        • Contact:
          • Anil Tombak
    • Terkirdag
      • Altınova, Terkirdag, Turkey (Türkiye)
        • Recruiting
        • Namik Kemal Universitesi Saglik Uygulama ve Arastirma Merkezi
        • Contact:
          • Seval Akapinar
        • Principal Investigator:
          • Seval Akapinar
    • İzmir
      • Bornova, İzmir, Turkey (Türkiye)
        • Recruiting
        • Ege Universitesi Tip Fakultesi
        • Principal Investigator:
          • Mahmut Tobu
  • United Kingdom
      • Belfast, United Kingdom, BT9 7AB
        • Withdrawn
        • Belfast City Hospital
      • Boston, United Kingdom
        • Recruiting
        • Pilgrim Hospital
        • Principal Investigator:
          • Ciro Rinaldi
        • Contact:
          • Ciro Rinaldi
      • London, United Kingdom, W12 0HS
        • Recruiting
        • Imperial College Healthcare NHS Trust
      • Milton Keynes, United Kingdom
        • Recruiting
        • Milton Keynes University Hospital
        • Contact:
          • Magbor Akanni
        • Principal Investigator:
          • Magbor Akanni
      • Oxford, United Kingdom
        • Recruiting
        • University of Oxford - The Weatherall Institute of Molecular Medicine (WIMM)
      • Southampton, United Kingdom
        • Recruiting
        • Southampton General Hospital
        • Principal Investigator:
          • Srinivasan Narayanan
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294-0001
        • Not yet recruiting
        • University of Alabama at Birmingham
    • California
      • Redlands, California, United States, 92373
        • Recruiting
        • Emad Ibrahim, MD, INC
    • Colorado
      • Englewood, Colorado, United States, 80113
        • Recruiting
        • US Oncology Inc
    • Maryland
      • Bethesda, Maryland, United States, 20852
        • Recruiting
        • American Oncology Partners of Maryland, PA
        • Contact:
          • Victor Priego
    • New York
      • New York, New York, United States, 10029
        • Recruiting
        • Icahn School Of Medicine At Mount Sinai
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • Recruiting
        • University of North Carolina at Chapel Hill
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Recruiting
        • The Cleveland Clinic Foundation
    • Oregon
      • Eugene, Oregon, United States, 97401
        • Recruiting
        • Oncology Associates of Oregon, P.C.
    • Texas
      • Houston, Texas, United States, 77030
        • Recruiting
        • MD Anderson Cancer Center
      • Houston, Texas, United States, 77089
        • Recruiting
        • Texas Oncology (Webster) - USOR
      • Sherman, Texas, United States, 75090
        • Recruiting
        • Texas Oncology-Denison Cancer Center
        • Principal Investigator:
          • Amir Faridi
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • University of Utah - Huntsman Cancer Institute - PPDS
    • Virginia
      • Roanoke, Virginia, United States, 43210
        • Recruiting
        • The James Cancer Hospital and Solove Research Institute
    • Washington
      • Seattle, Washington, United States, 98108-1532
        • Recruiting
        • VA Puget Sound Health Care System - NAVREF - PPDS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Givinostat - Core phase
Givinostat 50 mg BID from baseline till week 48
Drug: 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.
Other Names:
  • ITF2357
Active Comparator: Hydroxyurea - Core phase
HU 500 mg BID from baseline till week 48
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.
Other Names:
  • ITF2357

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients achieving a response at Week 48.
Time Frame: 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.
week 25 - week 48

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Proportion of patients achieving a complete hematological response (CHR) at Week 48.
Time Frame: 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
week 48
Time from randomization to the first observed CHR
Time Frame: Randomization - week 48
Randomization - week 48
Proportion of patients with a normal spleen size at Week 48.
Time Frame: week 48
week 48
Safety and tolerability up to Week 48.
Time Frame: Randomization - week 48
Randomization - week 48

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Italfarmaco

Collaborators

PPD Development, LP

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 26, 2024

Primary Completion (Estimated)

July 1, 2026

Study Completion (Estimated)

July 1, 2026

Study Registration Dates

First Submitted

October 10, 2023

First Submitted That Met QC Criteria

October 19, 2023

First Posted (Actual)

October 23, 2023

Study Record Updates

Last Update Posted (Actual)

March 25, 2026

Last Update Submitted That Met QC Criteria

March 24, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DSC/08/2357/32
  • 2022-502276-23-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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