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

NCT06093672 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: DSC/08/2357/322022-502276-23-00
• Study Type: interventional
• Target: 220
• Locations: 16 countries
• Sites: 90

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.

Conditions

Polycythemia Vera

Keywords

Polycythemia Vera; Givinostat

Outcome Measures

Primary Outcomes (1)

• Proportion of patients achieving a response at 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 Outcomes (4)

• Proportion of patients achieving a complete hematological response (CHR) at Week 48.

  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

• Safety and tolerability up to Week 48.

  Randomization - week 48

Study Arms (2)

Givinostat - Core phase

EXPERIMENTAL

Givinostat 50 mg BID from baseline till week 48

Drug: Givinostat

Hydroxyurea - Core phase

ACTIVE COMPARATOR

HU 500 mg BID from baseline till week 48

Drug: Hydroxyurea

Interventions

Givinostat 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.

Also known as: ITF2357

Givinostat - Core phase

Hydroxyurea 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.

Also known as: ITF2357

Hydroxyurea - Core phase

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Italfarmaco: lead
• PPD Development, LP: collaborator

Study Sites (90)

University of Alabama at Birmingham

Birmingham, Alabama, 35294-0001, United States

NOT YET RECRUITING

Emad Ibrahim, MD, Inc

Redlands, California, 92373, United States

RECRUITING

US Oncology Inc

Englewood, Colorado, 80113, United States

RECRUITING

American Oncology Partners of Maryland, PA

Bethesda, Maryland, 20852, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

RECRUITING

The Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

RECRUITING

Oncology Associates of Oregon, P.C.

Eugene, Oregon, 97401, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Texas Oncology (Webster) - USOR

Houston, Texas, 77089, United States

RECRUITING

Texas Oncology-Denison Cancer Center

Sherman, Texas, 75090, United States

RECRUITING

University of Utah - Huntsman Cancer Institute - PPDS

Salt Lake City, Utah, 84112, United States

RECRUITING

The James Cancer Hospital and Solove Research Institute

Roanoke, Virginia, 43210, United States

RECRUITING

VA Puget Sound Health Care System - NAVREF - PPDS

Seattle, Washington, 98108-1532, United States

RECRUITING

Landesklinikum Wiener Neustadt

Wiener Neustadt, Lower Austria, 2700, Austria

RECRUITING

Ordensklinikum Linz GmbH Elisabethinen

Linz, Upper Austria, 4020, Austria

RECRUITING

Klinikum Wels-Grieskirchen GmbH

Wels, Upper Austria, 4600, Austria

RECRUITING

Medizinische Universitat Wien (Medical University of Vienna)

Vienna, Vienna, 1090, Austria

RECRUITING

Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda

Sofia, Sofia-Grad, 1407, Bulgaria

RECRUITING

University Multiprofile Hospital for Active Treatment Sveti Georgi EAD

Plovdiv, 4001, Bulgaria

RECRUITING

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

Stara Zagora, 6003, Bulgaria

RECRUITING

Clinical Hospital Dubrava

Zagreb, City of Zagreb, 10000, Croatia

RECRUITING

Clinical Hospital Center Rijeka - PPDS

Rijeka, 51000, Croatia

RECRUITING

Clinical Hospital Center Rijeka

Rijeka, 51000, Croatia

NOT YET RECRUITING

General Hospital Sibenik

Šibenik, 22000, Croatia

NOT YET RECRUITING

Centre Hospitalier de Saint-Quentin

Saint-Quentin, Aisne, 2100, France

RECRUITING

CHU de Nice

Nice, Alpes-Maritimes, 6202, France

RECRUITING

Centre Hospitalier de Troyes

Troyes, Aube, 10000, France

RECRUITING

Hôpital Bretonneau

Tours, Indre-et-Loire, 37044, France

RECRUITING

CHU Nantes

Nantes, Loire-Atlantique, 44000, France

RECRUITING

CHU Angers

Angers, Maine-et-Loire, 49000, France

RECRUITING

CHU Amiens Hôpital Sud

Amiens, Somme, 80054, France

RECRUITING

Hôpital Saint Louis

Paris, 75010, France

RECRUITING

Hopital d'Argenteuil

Argenteuil, Île-de-France Region, 95107, France

RECRUITING

Medizinische Fakultät Mannheim der Universität Heidelberg, Universitätsmedizin Mannheim

Mannheim, Baden-Wurttemberg, 68167, Germany

RECRUITING

Gemeinschaftspraxis Hämatologie - Onkologie

Dresden, Saxony, 01307, Germany

RECRUITING

Universitätsmedizin Halle, Universitätsklinikum Halle, Klinik für Innere Medizin IV

Halle, Saxony-Anhalt, 06120, Germany

WITHDRAWN

OncoResearch Lerchenfeld GmbH

Hamburg, 22081, Germany

RECRUITING

Gyor-Moson-Sopron Vármegyei Petz Aladár Egyetemi Oktató Kórház

Győr, Győr-Moson-Sopron, 9024, Hungary

RECRUITING

Szabolcs-Szatmár-Bereg Vármegyei Oktatókórház

Nyíregyháza, Szabolcs-Szatmár-Bereg, 4400, Hungary

RECRUITING

Tolna Vármegyei Megyei Balassa János Kórház

Szekszárd, Tolna County, 7100, Hungary

RECRUITING

Cork University Hospital

Cork, Ireland

RECRUITING

Connolly Hospital Blanchardstown

Dublin, 15, Ireland

WITHDRAWN

Mater Misericordiae University Hospital

Dublin, 7, Ireland

RECRUITING

Hadassah Medical Center - PPDS

Jerusalem, Jerusalem, 91120, Israel

TERMINATED

Assuta Medical Center

Tel Aviv, Tel Aviv, 60000, Israel

RECRUITING

Bnai Zion Medical Center

Haifa, 31048, Israel

TERMINATED

Carmel Medical Center

Haifa, 34362, Israel

TERMINATED

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

Bari, Apulia, 70124, Italy

RECRUITING

Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli

Reggio Calabria, Calabria, 89133, Italy

RECRUITING

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

Bologna, Emilia-Romagna, 40138, Italy

RECRUITING

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

Meldola, Emilia-Romagna, 47014, Italy

RECRUITING

Azienda USL IRCCS di Reggio Emilia

Reggio Emilia, Emilia-Romagna, 42123, Italy

RECRUITING

Azienda Sanitaria Universitaria Friuli Centrale

Udine, Friuli Venezia Giulia, 33100, Italy

RECRUITING

Fondazione Policlinico Universitario Campus Bio-Medico di Roma

Rome, Lazio, 00128, Italy

RECRUITING

Azienda Ospedaliera Papa Giovanni XXIII

Bergamo, Lombardy, 24127, Italy

RECRUITING

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico

Milan, Lombardy, 20122, Italy

RECRUITING

Azienda Sanitaria Ospedaliera S. Croce e Carle

Cuneo, Piedmont, 12100, Italy

RECRUITING

A.O.U. Maggiore della Carità

Novara, Piedmont, 28100, Italy

RECRUITING

Azienda Ospedaliera Città della Salute e della Scienza di Torino

Turin, Piedmont, 10126, Italy

RECRUITING

Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco di Catania

Catania, Sicily, 95123, Italy

NOT YET RECRUITING

Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone

Palermo, Sicily, 90127, Italy

RECRUITING

Azienda Ospedaliero Universitaria delle Marche

Ancona, The Marches, 60126, Italy

RECRUITING

Azienda Ospedaliera Universitaria Careggi

Florence, Tuscany, 50134, Italy

RECRUITING

Spaarne Gasthuis

Hoofddorp, North Holland, 2134 TM, Netherlands

NOT YET RECRUITING

Medisch Spectrum Twente

Enschede, Overijssel, 7512 KZ, Netherlands

NOT YET RECRUITING

Albert Schweitzer Ziekenhuis

Dordrecht, South Holland, 3318 AT, Netherlands

NOT YET RECRUITING

Indywidualna Specjalistyczna Praktyka Lekarska Tomasz Woźny

Poznan, 60-549, Poland

RECRUITING

Specjalistyczny Szpital im. dra Alfreda Sokołowskiego

Wałbrzych, 58-309, Poland

RECRUITING

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza- Radeckiego we Wrocławiu

Wroclaw, 50-367, Poland

NOT YET RECRUITING

Clinical Hospital Center Bezanijska Kosa

Belgrade, 11000, Serbia

RECRUITING

Clinical Hospital Center Zemun

Belgrade, 11000, Serbia

RECRUITING

University Clinical Center of Serbia

Belgrade, 11000, Serbia

WITHDRAWN

University Clinical Center Nis

Niš, 18000, Serbia

RECRUITING

Clinical Center of Vojvodina

Novi Sad, 21000, Serbia

RECRUITING

ICO Badalona-H.U. Germans Trias i Pujol

Badalona, Barcelona, 8916, Spain

NOT YET RECRUITING

Hospital General Universitario Dr. Balmis

Alicante, 3010, Spain

WITHDRAWN

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

RECRUITING

Hospital Universitari i Politecnic La Fe de Valencia

Valencia, 46026, Spain

RECRUITING

Medical Park Bahcelievler Hastanesi

Bahçelievler, Istanbul, Turkey (Türkiye)

ENROLLING BY INVITATION

Ege Universitesi Tip Fakultesi

Bornova, İzmir, Turkey (Türkiye)

RECRUITING

VM Medical Park Mersin Hospital - Ataturk

Mezitli, Mersin, Turkey (Türkiye)

RECRUITING

Namik Kemal Universitesi Saglik Uygulama ve Arastirma Merkezi

Altınova, Terkirdag, Turkey (Türkiye)

RECRUITING

Belfast City Hospital

Belfast, BT9 7AB, United Kingdom

WITHDRAWN

Pilgrim Hospital

Boston, United Kingdom

RECRUITING

Imperial College Healthcare NHS Trust

London, W12 0HS, United Kingdom

RECRUITING

Milton Keynes University Hospital

Milton Keynes, United Kingdom

RECRUITING

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

Oxford, United Kingdom

RECRUITING

Southampton General Hospital

Southampton, United Kingdom

RECRUITING

MeSH Terms

Conditions

Polycythemia Vera

Interventions

givinostat; givinostat hydrochloride; Hydroxyurea

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Central Study Contacts

Maurizio Caserini

CONTACT

+39 02 6443 1; patientadvocacy@italfarmacogroup.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2023
• First Posted: October 23, 2023
• Study Start: March 26, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2026
• Last Updated: March 25, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (5); IL (4); IT (16); AU (4); DE (4); BU (3); NL (3); IE (3); GB (6); CR (4); PL (3); TU (4); US (14); FR (9); HU (3); ES (5)