Observational Study on the Use of Ropeginterferon Alfa-2b in Polycythemia Vera (ROPEG-PV)

Recruiting

• 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).

Study Timeline

• Study Start: 2022-09-08
• Study First Submitted: 2024-07-11
• Study First Submitted QC: 2024-07-11
• Study First Posted: 2024-07-17
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-31
• Last Update Posted: 2025-02-03
• Primary Completion: 2026-09-30
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 319

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

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 ≤ 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; 🇵🇱 Gdańsk, Poland

Pratia Onkologia, Department of Hematology and Cancer Prevention; 🇵🇱 Katowice, Poland

Jagiellonian University Hospital, Department of Haematology; 🇵🇱 Krakow, Poland

Copernicus Hospital; 🇵🇱 Lodz, Poland

Medical University, Clinical Department of Haematology, Blood Neoplasms and Bone Marrow Transplantation; 🇵🇱 Wrocław, Poland

UOC Ematologia, ASST Papa Giovanni XXIII; 🇮🇹 Bergamo, Lombardia, Italy

Divisione Ematologia ASST, Grande Ospedale Metropolitano Niguarda; 🇮🇹 Milano, Lombardia, Italy

Divisione Ematologia, Fondazione IRCCS Policlinico San Matteo; 🇮🇹 Pavia, Lombardia, Italy

U.O. Ematologia, Ospedale di Circolo e Fondazione Macchi Varese; 🇮🇹 Varese, Lombardia, Italy

Clinica Medica I Azienda Ospedaliera di Padova; 🇮🇹 Padova, Veneto, Italy

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