RecruitingPhase 3NCT06093672

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

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


Sponsor

Italfarmaco

Enrollment

220 participants

Start Date

Mar 26, 2024

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 Years

Inclusion Criteria13

  • 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:
  • if the patient received givinostat, a complete hematological response (CHR) at Week 48 shall be achieved
  • if the patient received HU, did not achieve a CHR (see above for the definition) at Week 48

Exclusion Criteria16

  • 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

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Interventions

DRUGGivinostat

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

DRUGHydroxyurea

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


Locations(90)

University of Alabama at Birmingham

Birmingham, Alabama, United States

Emad Ibrahim, MD, Inc

Redlands, California, United States

US Oncology Inc

Englewood, Colorado, United States

American Oncology Partners of Maryland, PA

Bethesda, Maryland, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

The Cleveland Clinic Foundation

Cleveland, Ohio, United States

Oncology Associates of Oregon, P.C.

Eugene, Oregon, United States

MD Anderson Cancer Center

Houston, Texas, United States

Texas Oncology (Webster) - USOR

Houston, Texas, United States

Texas Oncology-Denison Cancer Center

Sherman, Texas, United States

University of Utah - Huntsman Cancer Institute - PPDS

Salt Lake City, Utah, United States

The James Cancer Hospital and Solove Research Institute

Roanoke, Virginia, United States

VA Puget Sound Health Care System - NAVREF - PPDS

Seattle, Washington, United States

Landesklinikum Wiener Neustadt

Wiener Neustadt, Lower Austria, Austria

Ordensklinikum Linz GmbH Elisabethinen

Linz, Upper Austria, Austria

Klinikum Wels-Grieskirchen GmbH

Wels, Upper Austria, Austria

Medizinische Universitat Wien (Medical University of Vienna)

Vienna, Vienna, Austria

Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda

Sofia, Sofia-Grad, Bulgaria

University Multiprofile Hospital for Active Treatment Sveti Georgi EAD

Plovdiv, Bulgaria

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

Stara Zagora, Bulgaria

Clinical Hospital Dubrava

Zagreb, City of Zagreb, Croatia

Clinical Hospital Center Rijeka - PPDS

Rijeka, Croatia

Clinical Hospital Center Rijeka

Rijeka, Croatia

General Hospital Sibenik

Šibenik, Croatia

Centre Hospitalier de Saint-Quentin

Saint-Quentin, Aisne, France

CHU de Nice

Nice, Alpes-Maritimes, France

Centre Hospitalier de Troyes

Troyes, Aube, France

Hôpital Bretonneau

Tours, Indre-et-Loire, France

CHU Nantes

Nantes, Loire-Atlantique, France

CHU Angers

Angers, Maine-et-Loire, France

CHU Amiens Hôpital Sud

Amiens, Somme, France

Hôpital Saint Louis

Paris, France

Hopital d'Argenteuil

Argenteuil, Île-de-France Region, France

Medizinische Fakultät Mannheim der Universität Heidelberg, Universitätsmedizin Mannheim

Mannheim, Baden-Wurttemberg, Germany

Gemeinschaftspraxis Hämatologie - Onkologie

Dresden, Saxony, Germany

Universitätsmedizin Halle, Universitätsklinikum Halle, Klinik für Innere Medizin IV

Halle, Saxony-Anhalt, Germany

OncoResearch Lerchenfeld GmbH

Hamburg, Germany

Gyor-Moson-Sopron Vármegyei Petz Aladár Egyetemi Oktató Kórház

Győr, Győr-Moson-Sopron, Hungary

Szabolcs-Szatmár-Bereg Vármegyei Oktatókórház

Nyíregyháza, Szabolcs-Szatmár-Bereg, Hungary

Tolna Vármegyei Megyei Balassa János Kórház

Szekszárd, Tolna County, Hungary

Cork University Hospital

Cork, Ireland

Connolly Hospital Blanchardstown

Dublin, Ireland

Mater Misericordiae University Hospital

Dublin, Ireland

Hadassah Medical Center - PPDS

Jerusalem, Jerusalem, Israel

Assuta Medical Center

Tel Aviv, Tel Aviv, Israel

Bnai Zion Medical Center

Haifa, Israel

Carmel Medical Center

Haifa, Israel

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

Bari, Apulia, Italy

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

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

Azienda Sanitaria Universitaria Friuli Centrale

Udine, Friuli Venezia Giulia, Italy

Fondazione Policlinico Universitario Campus Bio-Medico di Roma

Rome, Lazio, Italy

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, Lombardy, Italy

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Lombardy, Italy

Azienda Sanitaria Ospedaliera S. Croce e Carle

Cuneo, Piedmont, Italy

A.O.U. Maggiore della Carità

Novara, Piedmont, Italy

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, Piedmont, Italy

Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco di Catania

Catania, Sicily, Italy

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, Sicily, Italy

Azienda Ospedaliero Universitaria delle Marche

Ancona, The Marches, Italy

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, Italy

Spaarne Gasthuis

Hoofddorp, North Holland, Netherlands

Medisch Spectrum Twente

Enschede, Overijssel, Netherlands

Albert Schweitzer Ziekenhuis

Dordrecht, South Holland, Netherlands

Indywidualna Specjalistyczna Praktyka Lekarska Tomasz Woźny

Poznan, Poland

Specjalistyczny Szpital im. dra Alfreda Sokołowskiego

Wałbrzych, Poland

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza- Radeckiego we Wrocławiu

Wroclaw, Poland

Clinical Hospital Center Bezanijska Kosa

Belgrade, Serbia

Clinical Hospital Center Zemun

Belgrade, Serbia

University Clinical Center of Serbia

Belgrade, Serbia

University Clinical Center Nis

Niš, Serbia

Clinical Center of Vojvodina

Novi Sad, Serbia

ICO Badalona-H.U. Germans Trias i Pujol

Badalona, Barcelona, Spain

Hospital General Universitario Dr. Balmis

Alicante, Spain

Hospital Universitario Ramon y Cajal

Madrid, Spain

Hospital Universitario Virgen de la Victoria

Málaga, Spain

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 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, United Kingdom

Pilgrim Hospital

Boston, United Kingdom

Imperial College Healthcare NHS Trust

London, 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

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