Monitoring Mutational Burden in Low Risk MDS Patients Using Sequential Peripheral Blood Samples

NCT04251078 | Recruiting

• 1 other identifier: N/A-NI-MDS-PI-13279
• Study Type: observational
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell malignancies. Somatic cytogenetic and molecular aberrations and the evolution of subclonal malignant cell populations are responsible for the development and progression of MDS into acute myeloid leukemia. Within only one decade the availability of new genome-wide technologies, like next generation sequencing (NGS), has revolutionized basic research. The routine clinical use of NGS analysis together with well-established diagnostic tools, like chromosome banding analysis or fluorescence in situ hybridization, will substantially add to existing diagnostic and prognostic criteria. This comprehensive combined approach could revolutionize the way we manage patient care. However, little is known about the application of such techniques in routine diagnostics and standards for such analyses are still missing. In a recent publication from the research group, (Article DOI: 10.1002/ajh.25089) it was demonstrated that the analysis of peripheral blood cells (at diagnosis) by NGS is feasible and yields data that are equivalent to the results obtained from bone marrow cells (BMC), which is currently the gold standard for most molecular diagnostic analyses. Not longer depending on the severe and for the patient painful collection of bone marrow aspirates now it is possible to perform comprehensive genetic analysis at short intervals on peripheral blood of MDS patients to detect and closely monitor patterns/pathways of clonal evolution of the malignant cell population in a routine diagnostic setting. It is expected that the obtained data from this study will substantially add to:

1. 1.Understand the functional relevance of identified mutations and the implications of combined mutations.
2. 2.Condense the findings from NGS together with data from established genetic methods (conventional cytogenetics, FISH) to a comprehensive view on MDS genetics and its dynamics considering strengths and weaknesses of each component of this approach.
3. 3.Demonstrate that peripheral blood could be an appropriate sample to perform NGS follow-up studies.

Conditions

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (3)

• SF3B1 status in the whole cohort (n=200)

  SF3B1 gene will be analyzed by Sanger sequencing in all cases.

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• Targeted deep sequencing analysis of MDS low risk cases that showed progression of the disease (n=20)

  Those cases that show progression of the disease will be retrospectively analyzed by NGS. Estimating that 10% of patients could progress, it is expected to include 10 new patients per year (during the two first years of the project) in the molecular analysis. This accounts a total of 20 patients after 2 years of follow-up. Targeted deep sequencing (panel of 40 myeloid related genes) will be performed in DNA from whole BM and PB paired samples at the moment of diagnosis and progression. Three PB follow-up samples in between will also be analyzed in order to track clonal dynamics. This accounts a total of 7 samples per each patient that progress.

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• Targeted deep sequencing analysis of MDS low risk cases that remained stable (no progression of the disease) (n=20)

  20 patients without progression will be analyzed in order to find out if there are any differences in the mutational spectrum compared with those disease progression cases. The same time points that were taken into account for those cases that progressed will be considered for these non-progression cases.

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Study Arms (2)

Myelodysplastic Syndromes - Progression cohort

According to the literature (Greenberg et al, Blood. 2012), around 5-15% are expected to progress to high/very high-risk MDS subtype or to acute myeloid leukemia (AML). According to the total cohort of patients, it is expected that 20 of them would comprise this group and will be studied by targeted deep sequencing.

Myelodysplastic Syndromes - Non Progression cohort

20 patients without progression will be analyzed by targeted deep sequencing in order to find out if there are any differences in the mutational spectrum compared with those disease progression cases.

Eligibility Criteria

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

Study Population

Taking into account the incidence of MDS in the area, it is planned to collect samples from 100 MDS patients per year (during the first 2 years of the project) categorized as very low, low and intermediate risk.

You may qualify if:

• Patients categorized as very low, low or intermediate risk according to the Revised International Prognosis Scoring System for MDS (IPSS-R).
• Patients that meet the previous criteria and are not receiving any treatment or are receiving supportive care only (erythropoietin is accepted).

You may not qualify if:

• Patients with "MDS with isolated del(5q)" diagnosis, according to 2017 World Health Organization Classification (WHO).
• Patients receiving any disease modifying therapies (e.g. hypomethylating agents).

Sponsors & Collaborators

• Josep Carreras Leukaemia Research Institute: lead
• Celgene: collaborator

Study Sites (1)

Josep Carreras Leukaemia Research Institute

Badalona, Barcelona, 08916, Spain

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Central Study Contacts

Francesc Sole, PhD

CONTACT

(+34) 93 557 28 06; fsole@carrerasresearch.org

Study Design

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

Study Record Dates

• First Submitted: January 30, 2020
• First Posted: January 31, 2020
• Study Start: January 1, 2019
• Primary Completion: June 1, 2025
• Study Completion: June 30, 2025
• Last Updated: February 21, 2025

Record last verified: 2025-02

Locations

ES (1)