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Unified platforM for a Better integRal Evaluation of MyeLodyspLastic Syndromes in SpAin-Strategy for Unraveling Personalized genoMic Medicine in Public heAlth System (UMBRELLA-SUMMA)

Recruiting
Conditions
Myelodysplastic Syndromes
Registration Number
NCT06379945
Lead Sponsor
Instituto de Investigación Biomédica de Salamanca
Brief Summary

Myelodysplastic Syndromes (MDS) are heterogeneous clonal diseases characterized by difficult diagnosis, complex prognostic stratification and unsatisfactory treatment. Based on that, UMBRELLA SUMMA aims to provide better clinical management and personalized medicine to MDS patients in Spain through improving diagnosis (1), prognosis (2 and 3), and treatment (2), and facilitating future investigations (4) of the disease.

More concretely, we propose: 1. The application of new technologies such as Optical Genome Mapping (OGM) in the diagnosis of those MDS cases whose cytogenetic alterations cannot be identify by other methods, as well as the implementation of this technology using peripheral blood avoiding more invasive methods for patients. 2. To provide all Spanish Group of MDS (GESMD) members who require it with the newly prognostic stratification of their patients (IPSS-M) by making Next Generation Sequencing (NGS) accessible for all of them. 3. Validate and improve a new prognostic system (AIPSS-MDS) previously developed within the GESMD, thanks to artificial intelligence, one of the tools with the most projection in the field of medicine currently. 4. To build and register ISCIII collections of cells, genetic material and/or plasma from all prospective MDS patients.

On the other hand, the dynamics of coexisting mutations in a specific context of chromosomal abnormalities could be defining the clinical fate of each patient. Based on that, the IBSAL team recently proposed three models of MDS evolution based on NGS data from three different cytogenetic subgroups: normal karyotype, trisomy 8 and 5q deletion. The IBSAL proposal aims to deepen into the pathophysiological mechanisms of MDS evolution in these three models through in vitro and in vivo functional studies and single-cell multiomics approaches.

Detailed Description

Myelodysplastic syndromes (MDS) are hematologic malignancies characterized by bone marrow dysplasia, cytopenias (anemia, infections, bleeding), and a high risk of progression to acute myeloid leukemia (AML). Diagnosis and prognostic stratification are challenging, and treatment outcomes remain suboptimal, especially in elderly patients, who represent the majority of cases.

Beyond structural cytogenetic abnormalities found in 40-70% of patients, over 90% of MDS cases harbor somatic mutations impacting cellular function. Next-generation sequencing (NGS) has improved diagnosis, prognostication, and therapeutic decision-making.

The Spanish Group of MDS (GESMD) brings together over 400 professionals across 100+ centers and maintains RESMD, the world's largest MDS patient registry. In 2020, GESMD launched UMBRELLA to provide NGS access to participating centers, addressing a key clinical gap.

Building on UMBRELLA's success, the UMBRELLA-SUMMA project will:

1. Implement Optical Genome Mapping (OGM) to enhance detection of chromosomal alterations, especially in cases where standard cytogenetics fail. We will explore the use of peripheral blood samples to minimize invasiveness.

2. Expand access to NGS to GESMD members lacking this technology, supporting prognostic classification based on the IPSS-M, an updated molecularly integrated scoring system.

3. Apply Artificial Intelligence (AI) to validate and improve a new AI-driven prognostic model for MDS developed within GESMD.

Additionally, the project will create biobanks of biological samples from GESMD patients, linked to clinical and epidemiological data within RESMD, ensuring optimal and regulated access for future research.

Given MDS heterogeneity, personalized medicine is essential. UMBRELLA-SUMMA will address this through the study of different patient subgroups (low-risk, high-risk, AML-transformed MDS) with a multidisciplinary team comprising clinicians, biologists, biotechnologists, and bioinformaticians.

Results will be disseminated among healthcare professionals, patients and their families via GESMD's patient resources, institutional websites, social media, and public engagement activities.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
300
Inclusion Criteria
  • Patients over 18 years old
  • Patients with a confirmed diagnosis of MDS by cytogenetics and/or morphological analysis
  • Patients with complete clinical data
  • Patients who sign the informed consent
Exclusion Criteria
  • Patients under 18 years old
  • Patients who do not sign the informed consent

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Mutations in MDSBaseline and follow up

Next Generation Sequencing will be use to define the IPSS-M (the International Molecular Prognostic Scoring System) in patients with MDS

Overall survival and leukemia-free survival in patients with MDSBaseline

The AIPSS-MDS (Artificial Intelligence Prognostic Scoring System for MDS) model will be validated to provide a personalized risk estimate for each individual patient

ISCIII collections of viable samplesBaseline

To build and register ISCIII collections of viable samples (PB and BM cells), genetic material and/or plasma from all prospective MDS patients

Structural variants and complex rearrangements in MDSBaseline

Optical Genome Mapping will be used to determine the presence of structural variant and complex rearrangements not detected by other conventional techniques

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (4)

Clínica Universitaria de Navarra

🇪🇸

Pamplona, Spain

Hospital Universitario Vall d´Hebron

🇪🇸

Barcelona, Spain

Fundación Instituto de Investigación Germans Trias i Puyol

🇪🇸

Badalona, Barcelona, Spain

Complejo Asistencial Universitario de Salamanca

🇪🇸

Salamanca, Spain

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