Clinical trial NCT06533813: Clinical Epidemiology in Contemporary Patients With Myelofibrosis.
Official title: Clinical Epidemiology in Contemporary Patients With Myelofibrosis (ERNEST-3): A European LeukemiaNet (ELN) Observational Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Myelofibrosis
Lead sponsor: FROM- Fondazione per la Ricerca Ospedale di Bergamo- ETS
Sponsor class: OTHER
Collaborators: name: GlaxoSmithKline
First posted: 2024-08-01
Enrollment: 617
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with a 2016- or 2022-WHO confirmed diagnosis of MF established from 01/01/2018 to 31/12/2027 will be enrolled into the study.

Patients with primary and secondary to ET and PV myelofibrosis, annotated for genetic and histological features, in relation to the presence of baseline (i.e., at MF diagnosis) or treatment-related cytopenias (i.e., reduced count of blood cells manifesting as anemia, thrombocytopenia and/or neutropenia).

Brief summary: Multicenter retrospective and prospective European observational study. At each site, all consecutive patients with a 2016- or 2022 World Health Organization (WHO) confirmed diagnosis of myelofibrosis (MF) established from 01/01/2018 to 31/12/2027 will be enrolled into the study. Yearly follow-up updates will be scheduled until the end of data collection on 31/12/2028 or until the last available patient visit, whichever comes first. At least 1 year of follow-up will be ensured from the last patient enrolled.

Detailed description: Myeloproliferative neoplasms (MPNs) are rare bone marrow disorders characterized by clonal proliferation of hematopoietic cell lineages, and include polycythemia vera (PV), essential thrombocythemia (ET), and myelofibrosis (MF). MF has worse prognosis, with main causes of death including acute leukemia transformation, comorbid conditions, and consequences of cytopenia. MF is characterized by progressive anemia, bone marrow fibrosis, and extramedullary hematopoiesis with splenomegaly. Moreover, the disease is associated with a heavy symptom burden including night sweats, fever, bone pain, and weight loss and worsening the quality of life.

On the beginning of 2013 the European Registry for Myeloproliferative Neoplasms (ERNEST) observational study was launched and approved by several IRBs of European hematological centers. The study focused on overt Primary (PMF) and Secondary myelofibrosis (SMF; i.e., post-Essential Thrombocythemia myelofibrosis (post-ET MF) and post-polycythemia (post-PV MF)) and aimed at describing the clinical epidemiology of large series of patients observed in clinical practice. This research was justified as the landscape of both pathophysiological and clinical knowledge in MPNs was rapidly evolving, prompting to revise diagnostic criteria, prognostication and therapy recommendations.

ERNEST retrospectively enrolled 1292 patients in whom the proposed prognostic models were confirmed to differentiate treatments in clinical practice, while ERNEST-2 reported results on critical events observed in 1010 of these cases during a median follow-up period of 5.4 years.4,5 The two studies closed in December 2022.

In the last decade, new diagnostic and prognostic findings have been accumulated and the availability of new approved drugs, based on results of several new clinical trials, influenced the therapy decision making in the real-world clinical practice. Therefore, the continuation of observational studies in present ERNEST-3 on large multicenter case series of patients with MF is timely and might refine the results of clinical trials.

The purpose of this study observational retrospective/prospective study is to gain information on MF associated cytopenias that represent a significant challenge in the contemporary patients with MF. Currently, there are few agents aimed at treating cytopenic MF, including immunomodulatory drugs, hypomethylating agents, and JAK inhibitors such as momelotinib and pacritinib, and development of new agents specifically tailored to this patient population remains an unmet need. Therefore, this study can provide data on these patients, focusing on clinical status, quality of life, comorbidities, and treatment results over time.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of primary myelofibrosis (PMF) or secondary (i.e., post-ET/PV MF) myelofibrosis according to 2016- or 2022-WHO criteria ascertained between 01/01/2018 and 31/12/2027
* Age ≥ 18 years
* Signed informed consent where applicable, in line with current European General Data Protection Regulation (GDPR) directives

Exclusion Criteria:

* Diagnosis of early/prefibrotic primary myelofibrosis
* Concurrent participation to interventional clinical trials in MF

Primary outcomes:
measure: Overall survival according to the presence of cytopenias at diagnosis
timeFrame: At diagnosis during the baseline
Secondary outcomes:
measure: Frequency and types of cytopenias
timeFrame: At baseline; 1 year follow-up.
measure: Treatments response and duration (according to modified IWG-MRT and ELN 2013 criteria, overall and by presence of cytopenias
timeFrame: At baseline; 1 year follow-up.
measure: Incidence of major CV events (thrombosis and bleeding), overall and by presence of cytopenias and treatments received
timeFrame: At baseline; 1 year follow-up.
measure: Incidence of disease progressions (MF accelerated phase, MF blast phase/acute myeloid leukemia (AML)), overall and by presence of cytopenias and treatments received
timeFrame: At baseline; 1 year follow-up.
measure: Incidence of secondary neoplasia, overall, by site and by presence of cytopenias and treatments received
timeFrame: At baseline; 1 year follow-up.
measure: Incidence of infections, overall and by presence of cytopenias and treatments received
timeFrame: At baseline; 1 year follow-up.
measure: Incidence of adverse events (AEs) of interest, overall, by type, severity and treatments received
timeFrame: At baseline; 1 year follow-up.
measure: Incidence of death, overall, by cause and by presence of cytopenias and treatments received
timeFrame: At baseline; 1 year follow-up.
Other outcomes:
Locations:
city: Yerevan
country: Armenia
facility: Hematology Center after Prof.R.H. Yeolyan
city: Copenhagen
country: Denmark
facility: University of Copenhagen's Roskilde Hospital
city: Paris
country: France
facility: Clinical Investigation Center of the Saint Louis Hospital
city: Greifswald
country: Germany
facility: Internal Medicine C, Hematology, Oncology, Stem Cell Transplantation and Palliative Care, University Medicine Greifswald
city: Halle
country: Germany
facility: University Hospital Halle Department of Hematology/Oncology
city: Minden
country: Germany
facility: University Clinic for Hematology, Oncology, Hemostaseology and Palliative Care Johannes Wesling Medical Center Minden UKRUB, University of Bochum
city: Ashdod
country: Israel
facility: Division of Haematology, Sasson University Hospital Assuta Ashdod, Ashdod, Ben-Gurion University of Negev
city: Alessandria
country: Italy
facility: A.S.O. SS. Antonio e Biagio e C.Arrigo, SC Ematologia
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII, SC Ematologia
city: Bologna
country: Italy
facility: Policlinico S. Orsola - Malpighi, Unità di Ematologia
city: Catania
country: Italy
facility: Azienda Ospedaliero - Universitaria "Policlinico Vittorio Emanuele" - PO Gaspare Rodolico, Dipartimento di ematologia con Trapianto di midollo Osseo
city: Firenze
country: Italy
facility: AOU Careggi di Firenze, Divisione di Ematologia
city: Milano
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda, Divisione 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: Fondazione IRCCS San Gerardo dei Tintori
city: Napoli
country: Italy
facility: Azienda Ospedaliera Universitaria Federico II, Divisione di Ematologia
city: Novara
country: Italy
facility: Azienda Ospedaliero Universitaria Maggiore della Carità, SCDU Ematologia
city: Padova
country: Italy
facility: Azienda Ospedale-Università di Padova, Dipartimento di Medicina
city: Padova
country: Italy
facility: Università degli Studi di Padova - Policlinico Universitario, Clinica Medica 1
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo, Divisione di 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: Torino
country: Italy
facility: A.O.U. Città della Salute e della Scienza di Torino - Ospedale Molinette- S.C. Ematologia U
city: Varese
country: Italy
facility: ASST dei Sette Laghi (Ospedale di Circolo e F. Macchi), Divisione U.O. Ematologia
city: Verona
country: Italy
facility: Azienda Ospedaliera Universitaria Integrata - Ospedale Borgo Roma, Unità di Ematologia
city: Vicenza
country: Italy
facility: Azienda ULSS 8 Berica - Ospedale San Bortolo, Divisione di Ematologia
city: Chisinau
country: Moldova, Republic of
facility: Institute of Oncology, State University of Medicine and Pharmacy - Department of Oncology, Hematology and Radiotherapy
city: Cracovia
country: Poland
facility: Department of Hematology, University Hospital, Jagiellonian University Medical College
city: Wrocław
country: Poland
facility: Department and Clinic of Haematology, Blood Neoplasms, and Bone Marrow Transplantation, Wroclaw Medical University
city: Bucharest
country: Romania
facility: Department of Hematology and Bone Marrow Transplantation, Fundeni Clinical Institute
city: Barcellona
country: Spain
facility: Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) - Hospital Clinic
city: Madrid
country: Spain
facility: Hematology and Hemotherapy Department, 12 de Octubre University Hospital
city: Valencia
country: Spain
facility: Servicio de Hematología - Hospital Clínico Universitario de Valencia
city: Belfast
country: United Kingdom
facility: School of Medicine, Dentistry and Biomedical Sciences Queen's University Belfast
city: Londra
country: United Kingdom
facility: Guy's and St. Thomas' NHS Foundation Trust.
Study officials:
affiliation: FROM- Fondazione per la Ricerca Ospedale di Bergamo- ETS
name: TIZIANO BARBUI, MD
role: STUDY_DIRECTOR
References: