Personalized Medicine Program on Myelodysplastic Syndromes: Characterization of the Patient's Genome for Clinical Decision Making and Systematic Collection of Real World Data to Improve Quality of Health Care

NCT04212390 | Completed

• 1 other identifier: FISIMMDS2020
• Study Type: observational
• Target: 1,000
• Locations: 1 country
• Sites: 2

Brief Summary

BACKGROUND Myelodysplastic syndromes (MDS) typically occur in elderly people and with time, a portion of the patients evolve into acute myeloid leukemia (AML). Therefore a risk-adapted treatment strategy is mandatory. Current prognostic scores present limitations, and in most cases fail to capture reliable prognostic information at individual level. STATE OF THE ART Important steps forward have been made in defining the molecular architecture of MDS and gene mutations have been reported to influence survival and risk of disease progression in MDS. Evaluation of the mutation status may add significant information to currently used prognostic scores and a comprehensive analyses of large, prospective patient populations is warranted to correctly estimate the independent effect of each mutation on clinical outcome and response to treatments. AIMS In this project, the investigators will develop a research platform by integrating genomic mutations, clinical variables and patient outcome derived from real-world data obtained from FISiM (Fondazione Italiana Sindromi Mielodisplastiche) clinical network, including 72 hematological centers. This will allow the investigators to:

1. 1.define the clinical utility of mutational screening in the diagnostic work-up and classification of MDS
2. 2.assess the implementation of diagnostic and therapeutic guidelines (appropriateness) in the real-life
3. 3.evaluate the impact of specific interventions (treatments) on clinical outcomes, long-term complications and costs
4. 4.identify predictors of response to specific treatments, and develop precision medicine programs in hematology based on Real World Evidence RWD
5. 5.measure patient-reported outcomes (PRO) and quality of life (QoL) in a real world MDS setting

Conditions

MDS (Myelodysplastic Syndrome)

Keywords

Personalized medicine; Gene mutations; Real-world evidence (RWE); Real world data (RWD)

Outcome Measures

Primary Outcomes (4)

• Type and frequency of recurrent gene mutations in MDS patients at diagnosis

  Polymorphonuclear granulocytes (PMN)/mononucleated cells (MNC) will be isolated from peripheral blood (PB) and/or bone marrow (BM) samples. Separated cells will be frozen locally and sent to the central lab to perform DNA extraction and NGS screening every 4 months.In all cases, a NGS screening will be performed by targeted approach to sequence all coding exons of 60 candidate genes. As a result of this approach, the investigators will describe type and frequency of recurrent gene mutations in MDS patients.

  0-24 months

• Prognostic significance of gene mutations in MDS patients

  A research platform will be developped by combining FISiM data on genetic and molecular characterization of hematological malignancies together with the national platform (REDCAP database), where clinical data are kept in a protected environment . The investigators will analyze the prognostic effect of gene mutations on MDS patients' outcome (overall survival) by multivariable analysis.

  12-36 months

• Measure of quality of life (QoL) in MDS patients

  The investigators will use QOL-E questionnaire to measure QoL in MDS patients. QOL-E is a specific tool to evaluate patient reported outcomes in patients with Myelodysplastic Syndromes. It evaluates the impact of the disease and treatment on 4 general dimensions (physical, functional, social and sexual well-being) and on one specific MDS-related dimension and also fatigue (https://qol-e.it/). Each item is rescaled so that a better response corresponds to a higher numerical value and better QoL.Transformation of raw scores into a 0-100 scale will be carried out to generate the standardized scores for each domain. Questionnaire will be completed by the patients upon study entry. Follow-up measurements will be performed every 6 months for patients receiving supportive care (including RBC transfusions), before and after disease modifying treatments (every 4 months) and at the time of disease progression.

  0-24 months

• Measure of patient-reported outcomes (PRO) in MDS patients.

  The investigators will use HM-PRO questionnaire (Hematology specific patient-reported outocome measure) to measure PRO in MDS patients. The HM-PRO is a composite measure consisting of two scales: Part A (mesures the impact of MDS and its treatment on a patient's quality of life; Part B (signs and symptoms, SS) captures the severity of different disease symptoms and treatment side effects (https://www.futuremedicine.com/doi/10.2217/cer-2018-0108?url\_ver=Z39.88-2003\&rfr\_id=ori%3Arid%3Acrossref.org\&rfr\_dat=cr\_pub%3Dwww.ncbi.nlm.nih.gov\&). Both scales have linear scoring system ranging from 0 to 100, with higher scores representing greater impact on QoL and symptom burden. Questionnaire will be completed by the patients upon study entry. Follow-up measurements will be performed every 6 months for patients receiving supportive care (including RBC transfusions), before and after disease modifying treatments (every 4 months) and at the time of disease progression.

  0-24 months

Study Arms (1)

FISiM MDS patients

Patients receiving a diagnosis of MDS and prospectively enrolled in the FISiM registry.

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Newly diagnosed patients affected with myelodysplastic syndromes (defined according to 2016 WHO classifcation criteria and stratified according to revised IPSS risk) prospectively enrolled in the FISiM registry

You may qualify if:

• Newly diagnosed patients affected with MDS:
• age ≥ 18 years
• written informed consent

You may not qualify if:

• Lack of written informed consent
• Lack of biological samples (peripheral blood, bone marrow aspirate)

Sponsors & Collaborators

• Fondazione Italiana Sindromi Mielodisplastiche-ETS: lead

Study Sites (2)

IRCCS Humanitas Research Hospital

Rozzano, Milano, 20089, Italy

Location

Elena Crisà

Candiolo, Torino, 10060, Italy

Location

Related Publications (19)

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Biospecimen

Retention: SAMPLES WITH DNA

Peripheral blood and marrow samples

MeSH Terms

Conditions

Anemia, Refractory, with Excess of Blasts

Condition Hierarchy (Ancestors)

Anemia, Refractory; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Myelodysplastic Syndromes; Bone Marrow Diseases

Study Officials

• Matteo Della Porta, MD

  Humanitas Hospital, Italy

  PRINCIPAL INVESTIGATOR

• Valeria Santini, MD

  AOU Careggi-Università di Firenze

  STUDY DIRECTOR

• Emanuele Angelucci, MD

  AOU San Martino IST - Genova

  STUDY DIRECTOR

• Enrico Balleari, MD

  AOU San Martino IST - Genova

  STUDY DIRECTOR

• Elena Crisà, MD

  l'AOU Maggiore della Carità di Novara

  STUDY DIRECTOR

• Pellgrino Musto, MD

  IRCCS Centro di Riferimento Oncologico della Basilicata Rionero in Vulture PZ

  STUDY DIRECTOR

• Antonella Poloni, MD

  Ospedali Riuniti - Università Politecnica delle Marche Ancona

  STUDY DIRECTOR

• Renato Zambello, MD

  U.O. Ematologia, Azienda Ospedale - Università di Padova

  STUDY DIRECTOR

• Lorenza Borin, MD

  ASST San Gerardo, Monza

  STUDY DIRECTOR

• Gastone Castellani, Physics

  University of Bologna

  STUDY DIRECTOR

• Pasquale Niscola, MD

  Ospedale S.Eugenio-CTO (ASL Roma 2), Roma

  STUDY DIRECTOR

• Esther Oliva, MD

  Ospedale Metropolitano Bianchi Melacrino Morelli di Reggio Calabria

  STUDY DIRECTOR

• Paolo Giorgio Sergio Pasini, Presidente AIPaSiM

  AIPaSiM, Associazione Italiana Pazienti con Sindrome Mielodisplastica

  STUDY DIRECTOR

• Francesco Passamonti, MD

  ASST Sette Laghi, Varese

  STUDY DIRECTOR

• Federica Pilo, MD

  Azienda Ospedaliera Brotzu, Cagliari

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: December 27, 2019
• Study Start: June 3, 2020
• Primary Completion: July 18, 2024
• Study Completion: July 18, 2024
• Last Updated: March 4, 2025

Record last verified: 2024-07

Locations

IT (2)