Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04251078
Recruitment Status : Recruiting
First Posted : January 31, 2020
Last Update Posted : January 31, 2020
Sponsor:
Collaborator:
Celgene
Information provided by (Responsible Party):
Josep Carreras Leukaemia Research Institute

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 we are now able 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. Understand the functional relevance of identified mutations and the implications of combined mutations.
  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. Demonstrate that peripheral blood could be an appropriate sample to perform NGS follow-up studies.

In a series of very low, low and intermediate risk MDS patients from Spain it is intended to retrospectively perform NGS (targeted deep sequencing) of diagnosis and consecutive follow-up samples selecting those cases that showed signs of progression of the disease.


Condition or disease
Myelodysplastic Syndromes

Show Show detailed description

Layout table for study information
Study Type : Observational
Estimated Enrollment : 200 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Monitoring Mutational Burden in Low Risk MDS Patients Using Sequential Peripheral Blood Samples
Actual Study Start Date : January 1, 2019
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : June 30, 2021

Resource links provided by the National Library of Medicine


Group/Cohort
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.



Primary Outcome Measures :
  1. SF3B1 status in the whole cohort (n=200) [ Time Frame: 1 day ]
    SF3B1 gene will be analyzed by Sanger sequencing in all cases.

  2. Targeted deep sequencing analysis of MDS low risk cases that showed progression of the disease (n=20) [ Time Frame: 1 day ]

    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.


  3. Targeted deep sequencing analysis of MDS low risk cases that remained stable (no progression of the disease) (n=20) [ Time Frame: 1 day ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
Criteria

Inclusion Criteria:

  • 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).

Exclusion Criteria:

  • 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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04251078


Contacts
Layout table for location contacts
Contact: Francesc Sole, PhD (+34) 93 557 28 06 fsole@carrerasresearch.org

Locations
Layout table for location information
Spain
Josep Carreras Leukaemia Research Institute Recruiting
Badalona, Barcelona, Spain, 08916
Contact: Francesc Sole, PhD    (+34) 93 557 28 06    fsole@carrerasresearch.org   
Sponsors and Collaborators
Josep Carreras Leukaemia Research Institute
Celgene
Layout table for additonal information
Responsible Party: Josep Carreras Leukaemia Research Institute
ClinicalTrials.gov Identifier: NCT04251078    
Other Study ID Numbers: N/A-NI-MDS-PI-13279
First Posted: January 31, 2020    Key Record Dates
Last Update Posted: January 31, 2020
Last Verified: January 2020

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Myelodysplastic Syndromes
Bone Marrow Diseases
Hematologic Diseases