Observational Study on the Use of Ropeginterferon Alfa-2b in Polycythemia Vera (ROPEG-PV)
- Conditions
- Polycythemia Vera
- Registration Number
- NCT06506084
- Lead Sponsor
- FROM- Fondazione per la Ricerca Ospedale di Bergamo- ETS
- Brief Summary
Polycythaemia vera (PV) is associated with a reduced quality of life, a high rate of vascular events, and an intrinsic risk of disease evolution. The results of several randomised trials for the treatment with new cytoreductive agents are now available, among which a new ropegylated formulation of interferon alfa-2b (ropeginterferon alfa-2b) have been recently approved in Europe and USA \[EMA (2019), FDA (2021) and AIFA (2022)\]. The use of this drug in clinical practice is an opportunity for a prospective observational study in a rare disease such as PV; the aim is to evaluate its impact in the practical management of these patients.
Therefore, the main objectives of the present study are to determine:
(i) to what extent ropeginterferon alfa-2b can be prescribed and tolerated in patients with PV; (ii) the risk-benefit of ropeginterferon alfa-2b in patients with PV, followed-up in real-world clinical practice.
- Detailed Description
Classical Philadelphia-negative myeloproliferative neoplasms (Ph-neg MPNs) including polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF) are characterized by uncontrolled clonal proliferation of multipotent bone marrow progenitors, sustained by acquired mutations in JAK2, CALR and MPL genes.
Natural history of PV is marked by life threatening outcomes such as thrombosis, bleeding and clonal evolution towards myelofibrosis and acute myeloid leukemia. Treatment-relevant risk stratification is designed to estimate the likelihood of thrombotic complications, which is estimated to occur before or after diagnosis in 20-30% of patients according disease and patient-related risk factors. The cornerstone of treatment in PV includes scheduled phlebotomy, with a hematocrit (Hct) target of \<45% and low-dose aspirin in all patients, regardless of risk category. There is currently broad consensus regarding the need for cytoreductive drugs in high-risk patients with PV identified by age \>60 years and prior history of thrombosis.
The results of several andomized trials for the treatment of PV are now available, and, in addition to the standard drug hydroxyurea (HU), both a new ropegylated formulation of interferon alfa-2b3 and ruxolitinib4 are now available have been approved in Europe and US and European LeukemiaNet (ELN) investigators have recently provided recommendations for the use of these drugs in clinical practice in low-risk as well as high-risk patients.
After approval by EMA (2019) and FDA (2021), the drug (ROPEGINTERFERON ALFA-2B) was very recently approved and reimbursed by AIFA (2022) in some subgroups of patients with PV. The use of this drug in clinical practice is an opportunity for a prospective observational study in a rare disease such as PV; the aim is to evaluate its impact in the practical management of these patients, according to Determinazione AIFA 20 marzo 2008 about observational clinical studies, and Decreto Ministeriale 17 dicembre 2004 on non-profit studies.
It is not entirely known which is the percentage of patients who, after careful screening as required in good clinical practice, will fail the indications for concomitant clinical or laboratory abnormalities. Furthermore, the proportion of patients who discontinue the drug during follow-up for intolerance or other reasons is currently unknown and data on the benefit-risk ratio are limited.
Moreover, it should be noted that the haematological and clinical responses obtained in clinical trials not always are replicated in the studies of the real-world clinical practice. In fact, daily management of PV patients does not require the same stringent enrollment and follow-up criteria as instead are necessary in clinical trials. Our proposal may also contribute to better implement the results following the recent guidelines, particularly in some subgroups of patients in which AIFA has established the use with reimbursement by Italian National Health System (NHS) (i.e., patients intolerant to HU, women of childbearing age who plan pregnancy and patients with history of skin cancer).
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 319
- Patients diagnosed with Polycythemia Vera by WHO 2016
- Patient aged โฅ 18 years old
- Patients in need of cytoreductive treatments with ropeginterferon alfa-2b in first or later lines according to the reimbursability criteria defined by the Italian National Health System
- Patients who have signed the written informed consent for study participation.
โข Any contraindication for ropeginterferon alfa-2b according to the SmPC
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Complete hematological remission (CHR)* after 1 and 2 years of treatment. At baseline and during the follow up at 6/12/18/24 months per patient. \*HCT lower than 45% without phlebotomies in the past 3 months; platelet count โค 400x109/L, WBC count \<10 x109/L
- Secondary Outcome Measures
Name Time Method Complete hematological (CHR) and clinical remission (CR) after 1 and 2 years of treatment stratified by different eligibility categories for treatment indication. At baseline and during the follow up at 6/12/18/24 months per patient. Secondary Outcomes for efficacy
Frequency of phlebotomies At baseline and during the follow up at 6/12/18/24 months per patient. Secondary Outcomes for efficacy
Change in spleen size At baseline and during the follow up at 6/12/18/24 months per patient. Change in spleen size (from baseline) evaluated by palpation.
Incidence, causality and intensity of any adverse event occurring during study period (as defined by MedDRA code and graded according to Common Terminology Criteria for Adverse Events (CTCAE last version)). At baseline and during the follow up at 6/12/18/24 months per patient. Secondary Outcomes for safety
Screening failure At baseline and during the follow up at 6/12/18/24 months per patient. Percentage of patients who, after careful screening as required in good clinical practice, will fail the indications for concomitant clinical or laboratory abnormalities.
Dose-response effect on CHR and CR At baseline and during the follow up at 6/12/18/24 months per patient. Secondary Outcomes for efficacy
Incidence of any of the following: o arterial and venous thrombotic events; o hemorrhagic events; o disease related symptoms; o disease evolutions into myelofibrosis and acute leukemia; o secondary malignancies. At baseline and during the follow up at 6/12/18/24 months per patient. Secondary Outcomes for efficacy
Trial Locations
- Locations (37)
University Medical Center, Department of Hematology and Transplantation
๐ต๐ฑGdaลsk, Poland
Pratia Onkologia, Department of Hematology and Cancer Prevention
๐ต๐ฑKatowice, Poland
Jagiellonian University Hospital, Department of Haematology
๐ต๐ฑKrakow, Poland
Copernicus Hospital
๐ต๐ฑLodz, Poland
Medical University, Clinical Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation
๐ต๐ฑWrocลaw, Poland
UOC Ematologia, ASST Papa Giovanni XXIII
๐ฎ๐นBergamo, Lombardia, Italy
Divisione Ematologia ASST, Grande Ospedale Metropolitano Niguarda
๐ฎ๐นMilano, Lombardia, Italy
Divisione Ematologia, Fondazione IRCCS Policlinico San Matteo
๐ฎ๐นPavia, Lombardia, Italy
U.O. Ematologia, Ospedale di Circolo e Fondazione Macchi Varese
๐ฎ๐นVarese, Lombardia, Italy
Clinica Medica I Azienda Ospedaliera di Padova
๐ฎ๐นPadova, Veneto, Italy
Divisione Ematologia, Ospedale Borgo Roma
๐ฎ๐นVerona, Veneto, Italy
Divisione Ematologia, Ospedale San Bortolo
๐ฎ๐นVicenza, Veneto, Italy
A.S.O. SS. Antonio e Biagio e C.Arrigo di Alessandria
๐ฎ๐นAlessandria, Italy
Azienda Ospedaliera Universitaria Consorziale - Policlinico, U.O. Ematologia con Trapianto
๐ฎ๐นBari, Italy
Policlinico S. Orsola - Malpighi, Unitร di Ematologia
๐ฎ๐นBologna, Italy
ASST-Spedali Civili
๐ฎ๐นBrescia, Italy
Ospedale Businco, S.C. Ematologia e CTMO
๐ฎ๐นCagliari, Italy
Azienda Ospedaliero - Universitaria "Policlinico Vittorio Emanuele" - PO Gaspare Rodolico, Dipartimento di Ematologia con Trapianto di midollo Osseo
๐ฎ๐นCatania, Italy
Azienda Ospedaliera S. Croce e Carle di Cuneo- Divisione di Ematologia,
๐ฎ๐นCuneo, Italy
Arcispedale Sant'Anna Azienda Ospedaliero - Universitaria di Ferrara, Unitร Operativa di Ematologia
๐ฎ๐นFerrara, Italy
Azienda Ospedaliera Universitaria Careggi, Divisione di Ematologia
๐ฎ๐นFirenze, Italy
Azienda Ospedaliera Universitaria Policlinico "G. Martino", UOC Ematologia
๐ฎ๐นMessina, Italy
Ospedale dell'Angelo, Dipartimento di Ematologia
๐ฎ๐นMestre, Italy
Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Ematologia
๐ฎ๐นMilano, Italy
Ospedale San Raffaele, Unitร Operativa di Ematologia e Trapianto Midollo Osseo
๐ฎ๐นMilano, Italy
ASST MONZA Ospedale San Gerardo Clinica Ematologica
๐ฎ๐นMonza, Italy
Azienda Ospedaliera Universitaria Federico II di Napoli Divisione di Ematologia e Trapianti del Midollo
๐ฎ๐นNapoli, Italy
Azienda Ospedaliero Universitaria Maggiore della Caritร di Novara SCDU Ematologia
๐ฎ๐นNovara, Italy
Azienda Ospedaliera Universitaria Policlinico "P. Giaccone", Divisione di Ematologia
๐ฎ๐นPalermo, Italy
Azienda Ospedaliera Universitaria Pisana
๐ฎ๐นPisa, Italy
Azienda Ospedaliera San Eugenio - UOC Ematologia
๐ฎ๐นRoma, Italy
Fondazione Policlinico Universitario A. Gemelli - Universitร Cattolica del Sacro Cuore, UCSC Ematologia
๐ฎ๐นRoma, Italy
Policlinico Umberto I, Dipartimento Ematologia, Oncologia e Dermatologia
๐ฎ๐นRoma, Italy
Ospedale Casa Sollievo della Sofferenza Istituto di Ricovero e Cura a Carattere Scientifico, U.O. Ematologia
๐ฎ๐นSan Giovanni Rotondo, Italy
A.O.U. Cittร della Salute e della Scienza di Torino - Ospedale Molinette- S.C. Ematologia U
๐ฎ๐นTorino, Italy
Ospedale Maggiore, SC Ematologia
๐ฎ๐นTrieste, Italy
Azienda Sanitaria Universitaria Integrata, Presidio Ospedaliero "Santa Maria della Misericordia", Clinica Ematologica
๐ฎ๐นUdine, Italy