Clinical trial NCT06506084: Observational Study on the Use of Ropeginterferon Alfa-2b in Polycythemia Vera (ROPEG-PV)
Official title: Observational Study on the Use of Ropeginterferon Alfa-2b in Polycythemia Vera (ROPEG-PV)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Polycythemia Vera
Lead sponsor: FROM- Fondazione per la Ricerca Ospedale di Bergamo- ETS
Sponsor class: OTHER
First posted: 2024-07-17
Enrollment: 319
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The first time point to assess the primary outcome defined as the achievement of CHR is after 12 months of treatment with ropeginterferon alfa-2b, is reasonable to provide evidence of at least a non-inferiority in terms of CHR with this new drug. In this framework, a sample size is calculated to test 1-sample non-inferiority of a proportion. Setting the expected proportion p of CHR under ropeginterferon alfa-2b equals to the reference value (p0) obtained with ruxolitinib (i.e., p = p0 = 0.24), a sample size of 319 is needed to demonstrate that the proportion of CHR under ropeginterferon alfa-2b is not inferior to that obtained under ruxolitinib, allowing a margin of non-inferiority (delta) of 0.07 and assuming alpha and beta errors of 5% and 10%, respectively.

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).

Eligibility criteria: Inclusion Criteria:

* Patients diagnosed with Polycythemia Vera by WHO 2016
* Patient aged ≥ 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.

Exclusion Criteria:

• Any contraindication for ropeginterferon alfa-2b according to the SmPC

Primary outcomes:
measure: Complete hematological remission (CHR)* after 1 and 2 years of treatment.
timeFrame: At baseline and during the follow up at 6/12/18/24 months per patient.
Secondary outcomes:
measure: Screening failure
timeFrame: At baseline and during the follow up at 6/12/18/24 months per patient.
measure: Complete hematological (CHR) and clinical remission (CR) after 1 and 2 years of treatment stratified by different eligibility categories for treatment indication.
timeFrame: At baseline and during the follow up at 6/12/18/24 months per patient.
measure: Dose-response effect on CHR and CR
timeFrame: At baseline and during the follow up at 6/12/18/24 months per patient.
measure: Frequency of phlebotomies
timeFrame: At baseline and during the follow up at 6/12/18/24 months per patient.
measure: Change in spleen size
timeFrame: At baseline and during the follow up at 6/12/18/24 months per patient.
measure: 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.
timeFrame: At baseline and during the follow up at 6/12/18/24 months per patient.
measure: 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)).
timeFrame: At baseline and during the follow up at 6/12/18/24 months per patient.
Other outcomes:
Locations:
city: Bergamo
country: Italy
facility: UOC Ematologia, ASST Papa Giovanni XXIII
state: Lombardia
city: Milano
country: Italy
facility: Divisione Ematologia ASST, Grande Ospedale Metropolitano Niguarda
state: Lombardia
city: Pavia
country: Italy
facility: Divisione Ematologia, Fondazione IRCCS Policlinico San Matteo
state: Lombardia
city: Varese
country: Italy
facility: U.O. Ematologia, Ospedale di Circolo e Fondazione Macchi Varese
state: Lombardia
city: Padova
country: Italy
facility: Clinica Medica I Azienda Ospedaliera di Padova
state: Veneto
city: Verona
country: Italy
facility: Divisione Ematologia, Ospedale Borgo Roma
state: Veneto
city: Vicenza
country: Italy
facility: Divisione Ematologia, Ospedale San Bortolo
state: Veneto
city: Alessandria
country: Italy
facility: A.S.O. SS. Antonio e Biagio e C.Arrigo di Alessandria
city: Bari
country: Italy
facility: Azienda Ospedaliera Universitaria Consorziale - Policlinico, U.O. Ematologia con Trapianto
city: Bologna
country: Italy
facility: Policlinico S. Orsola - Malpighi, Unità di Ematologia
city: Brescia
country: Italy
facility: ASST-Spedali Civili
city: Cagliari
country: Italy
facility: Ospedale Businco, S.C. Ematologia e CTMO
city: Catania
country: Italy
facility: Azienda Ospedaliero - Universitaria "Policlinico Vittorio Emanuele" - PO Gaspare Rodolico, Dipartimento di Ematologia con Trapianto di midollo Osseo
city: Cuneo
country: Italy
facility: Azienda Ospedaliera S. Croce e Carle di Cuneo- Divisione di Ematologia,
city: Ferrara
country: Italy
facility: Arcispedale Sant'Anna Azienda Ospedaliero - Universitaria di Ferrara, Unità Operativa di Ematologia
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi, Divisione di Ematologia
city: Messina
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico "G. Martino", UOC Ematologia
city: Mestre
country: Italy
facility: Ospedale dell'Angelo, Dipartimento di Ematologia
city: Milano
country: Italy
facility: Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico, Ematologia
city: Milano
country: Italy
facility: Ospedale San Raffaele, Unità Operativa di Ematologia e Trapianto Midollo Osseo
city: Monza
country: Italy
facility: ASST MONZA Ospedale San Gerardo Clinica Ematologica
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II di Napoli Divisione di Ematologia e Trapianti del Midollo
city: Novara
country: Italy
facility: Azienda Ospedaliero Universitaria Maggiore della Carità di Novara SCDU Ematologia
city: Palermo
country: Italy
facility: Azienda Ospedaliera Universitaria Policlinico "P. Giaccone", Divisione di Ematologia
city: Pisa
country: Italy
facility: Azienda Ospedaliera Universitaria Pisana
city: Roma
country: Italy
facility: Azienda Ospedaliera San Eugenio - UOC Ematologia
city: Roma
country: Italy
facility: Fondazione Policlinico Universitario A. Gemelli - Università Cattolica del Sacro Cuore, UCSC Ematologia
city: Roma
country: Italy
facility: Policlinico Umberto I, Dipartimento Ematologia, Oncologia e Dermatologia
city: San Giovanni Rotondo
country: Italy
facility: Ospedale Casa Sollievo della Sofferenza Istituto di Ricovero e Cura a Carattere Scientifico, U.O. Ematologia
city: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino - Ospedale Molinette- S.C. Ematologia U
city: Trieste
country: Italy
facility: Ospedale Maggiore, SC Ematologia
city: Udine
country: Italy
facility: Azienda Sanitaria Universitaria Integrata, Presidio Ospedaliero "Santa Maria della Misericordia", Clinica Ematologica
city: Gdańsk
country: Poland
facility: University Medical Center, Department of Hematology and Transplantation
city: Katowice
country: Poland
facility: Pratia Onkologia, Department of Hematology and Cancer Prevention
city: Krakow
country: Poland
facility: Jagiellonian University Hospital, Department of Haematology
city: Lodz
country: Poland
facility: Copernicus Hospital
city: Wrocław
country: Poland
facility: Medical University, Clinical Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation
Study officials:
affiliation: FROM- Fondazione per la Ricerca Ospedale di Bergamo- ETS
name: TIZIANO BARBUI, MD
role: STUDY_DIRECTOR
References: