Clinical trial NCT06093672: Study on Efficacy and Safety of Givinostat Versus Hydroxyurea in Patients With Polycythemia Vera
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Polycythemia Vera
Lead sponsor: Italfarmaco
Sponsor class: INDUSTRY
First posted: 2023-10-23
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* Patients must have been diagnosed with PV according to the 2016 WHO criteria within 3 years before randomization
* Patients must have JAK2V617F-positive disease
* Patients with PV must meet the definition of HR for thrombosis (i.e., HR) at 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

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

Primary outcomes:
measure: Proportion of patients achieving a response at Week 48.
timeFrame: week 25 - week 48
Secondary outcomes:
measure: Proportion of patients achieving a complete hematological response (CHR) at Week 48.
timeFrame: week 48
measure: Time from randomization to the first observed CHR
timeFrame: Randomization - week 48
measure: Proportion of patients with a normal spleen size at Week 48.
timeFrame: week 48
measure: Safety and tolerability up to Week 48.
timeFrame: Randomization - week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Redlands
country: United States
facility: Emad Ibrahim, MD, Inc
state: California
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: Cleveland
country: United States
facility: The Cleveland Clinic Foundation
state: Ohio
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah - Huntsman Cancer Institute - PPDS
state: Utah
city: Seattle
country: United States
facility: VA Puget Sound Health Care System - NAVREF - PPDS
state: Washington
city: Wiener Neustadt
country: Austria
facility: Landesklinikum Wiener Neustadt
state: Niederösterreich
city: Linz
country: Austria
facility: Ordensklinikum Linz GmbH Elisabethinen
state: Oberösterreich
city: Wels
country: Austria
facility: Klinikum Wels-Grieskirchen GmbH
state: Oberösterreich
city: Vienna
country: Austria
facility: Medizinische Universitat Wien (Medical University of Vienna)
state: Wien
city: Sofia
country: Bulgaria
facility: Acibadem City Clinic Multiprofile Hospital for Active Treatment Tokuda
state: Sofia-Grad
city: Plovdiv
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment Sveti Georgi EAD
city: Stara Zagora
country: Bulgaria
facility: University Multiprofile Hospital for Active Treatment - Prof. Dr. Stoyan Kirkovich AD
city: Zagreb
country: Croatia
facility: Clinical Hospital Center Zagreb
state: Grad Zagreb
city: Zagreb
country: Croatia
facility: Clinical Hospital Dubrava
state: Grad Zagreb
city: Rijeka
country: Croatia
facility: Clinical Hospital Center Rijeka
city: Šibenik
country: Croatia
facility: General Hospital Sibenik
city: Saint-Quentin
country: France
facility: Centre Hospitalier de Saint-Quentin
state: Aisne
city: Nice
country: France
facility: CHU de Nice
state: Alpes-Maritimes
city: Troyes
country: France
facility: Centre Hospitalier de Troyes
state: Aube
city: Tours
country: France
facility: Hôpital Bretonneau
state: Indre-et-Loire
city: Nantes
country: France
facility: CHU Nantes
state: Loire-Atlantique
city: Angers
country: France
facility: CHU Angers
state: Maine-et-Loire
city: Amiens
country: France
facility: CHU Amiens Hôpital Sud
state: Somme
city: Paris
country: France
facility: Hôpital Saint Louis
city: Argenteuil
country: France
facility: Hopital d'Argenteuil
state: Île-de-France
city: Mannheim
country: Germany
facility: Medizinische Fakultät Mannheim der Universität Heidelberg, Universitätsmedizin Mannheim
state: Baden-Württemberg
city: Halle (Saale)
country: Germany
facility: Universitätsmedizin Halle, Universitätsklinikum Halle, Klinik für Innere Medizin IV
state: Sachsen-Anhalt
city: Dresden
country: Germany
facility: Gemeinschaftspraxis Hämatologie - Onkologie
state: Sachsen
city: Hamburg
country: Germany
facility: OncoResearch Lerchenfeld GmbH
city: Székesfehérvár
country: Hungary
facility: Fejer Varmegyei Szent Gyorgy Egyetemi Oktato Korhaz
state: Fejer
city: Győr
country: Hungary
facility: Gyor-Moson-Sopron Vármegyei Petz Aladár Egyetemi Oktató Kórház
state: Győr-Moson-Sopron
city: Nyíregyháza
country: Hungary
facility: Szabolcs-Szatmár-Bereg Vármegyei Oktatókórház
state: Szabolcs-Szatmár-Bereg
city: Szekszárd
country: Hungary
facility: Tolna Vármegyei Megyei Balassa János Kórház
state: Tolna
city: Cork
country: Ireland
facility: Cork University Hospital
city: Dublin
country: Ireland
facility: Connolly Hospital Blanchardstown
city: Dublin
country: Ireland
facility: Mater Misericordiae University Hospital
city: Tel Aviv-Yafo
country: Israel
facility: Assuta Medical Center
state: Tel-Aviv
city: Jerusalem
country: Israel
facility: Hadassah Medical Center - PPDS
state: Yerushalayim
city: Haifa
country: Israel
facility: Bnai Zion Medical Center
city: Haifa
country: Israel
facility: Carmel Medical Center
city: Reggio Calabria
country: Italy
facility: Grande Ospedale Metropolitano Bianchi-Melacrino-Morelli
state: Calabria
city: Bologna
country: Italy
facility: Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere Scientifico
state: Emilia-Romagna
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l
state: Emilia-Romagna
city: Reggio Emilia
country: Italy
facility: Azienda USL IRCCS di Reggio Emilia
state: Emilia-Romagna
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Friuli Centrale
state: Friuli-Venezia Giulia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario Campus Bio-Medico di Roma
state: Lazio
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Papa Giovanni XXIII
state: Lombardia
city: Milano
country: Italy
facility: Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
state: Lombardia
city: Ancona
country: Italy
facility: Azienda Ospedaliero Universitaria delle Marche
state: Marche
city: Cuneo
country: Italy
facility: Azienda Sanitaria Ospedaliera S. Croce e Carle
state: Piemonte
city: Novara
country: Italy
facility: A.O.U. Maggiore della Carità
state: Piemonte
city: Torino
country: Italy
facility: Azienda Ospedaliera Città della Salute e della Scienza di Torino
state: Piemonte
city: Bari
country: Italy
facility: Istituto Tumori "Giovanni Paolo II" I.R.C.C.S.
state: Puglia
city: Catania
country: Italy
facility: Azienda Ospedaliero Universitaria Policlinico G Rodolico San Marco di Catania
state: Sicilia
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone
state: Sicilia
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
state: Toscana
city: Hoofddorp
country: Netherlands
facility: Spaarne Gasthuis
state: Noord-Holland
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
state: Overijssel
city: Dordrecht
country: Netherlands
facility: Albert Schweitzer Ziekenhuis
state: Zuid-Holland
city: Poznań
country: Poland
facility: Indywidualna Specjalistyczna Praktyka Lekarska Tomasz Woźny
city: Wałbrzych
country: Poland
facility: Specjalistyczny Szpital im. dra Alfreda Sokołowskiego
city: Wrocław
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza- Radeckiego we Wrocławiu
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanijska Kosa
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Zemun
city: Belgrade
country: Serbia
facility: University Clinical Center of Serbia
city: Nis
country: Serbia
facility: University Clinical Center Nis
city: Novi Sad
country: Serbia
facility: Clinical Center of Vojvodina
city: Badalona
country: Spain
facility: ICO Badalona-H.U. Germans Trias i Pujol
state: Barcelona
city: Alicante
country: Spain
facility: Hospital General Universitario Dr. Balmis
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Málaga
country: Spain
facility: Hospital Universitario Virgen de la Victoria
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
city: Belfast
country: United Kingdom
facility: Belfast City Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
References: