Screening and Genetic Monitoring of Patients With Myelodysplastic Syndromes (MDS) Under Different Treatment Modalities by Cytogenetic Analyses of Circulating CD34+Cells

February 20, 2020 updated by: Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH

Screening and Genetic Monitoring of Patients With MDS Under Different Treatment Modalities by Cytogenetic Analyses of Circulating CD34+Cells

In myelodysplastic syndromes (MDS) the knowledge about chromosomal aberrations is important for diagnosis, pathogenesis, prognosis and treatment. Usually, chromosomal anomalies in MDS patients are detected in bone marrow cells by chromosome banding analyses of metaphases. Alternatively or additionally they can be diagnosed by Fluorescence-in-Situ-Hybridization (FISH). The investigators here present a novel method for cytogenetic monitoring of MDS patients from peripheral blood which is representative for the clone size in bone marrow cells. The purpose of this prospective multicenter non-interventional diagnostic study is to detect and to follow chromosomal aberrations from peripheral blood closely, to assess karyotype evolution, to detect rare abnormalities and to correlate the molecular-cytogenetic results with peripheral blood counts, bone marrow morphology and treatment modalities and responses.

Study Overview

Status

Completed

Conditions

Detailed Description

Chromosomal aberrations in myelodysplastic syndromes (MDS) play a major role in diagnostics, pathogenesis, prognosis, and, more recently, in treatment allocations. Chromosomal anomalies can be detected by conventional chromosome banding analyses of bone marrow metaphases and most of them are provable by Fluorescence in situ hybridization (FISH) of circulating CD34+ progenitor cells from peripheral blood. For this prospective multicenter non-interventional diagnostic study sequential FISH analyses are performed on immunomagnetically enriched circulating CD34+ cells from peripheral blood as follows: A "super-panel" with the probes D7/CEP7, EGR1, CEP8, CEP XY, D20, p53, IGH/BCL2, TEL/AML1, RB1, MLL, 1p36/1q25, CSF1R (all Abbott® probes) is used for initial screening, every 12 months during follow-up and in every case of suspected progression. A smaller "standard-panel" with the probes EGR1, D7/CEP7, CEP8, p53, D20, CEP X/Y, TEL/AML1 - plus if necessary an informative probe of the superpanel- was performed for analyses at short intervals every 2 months in the 1st year and every 3 months during the 2nd and 3rd year. Peripheral blood counts are documented once a month, and full blood counts with the number of peripheral blasts are recommended at the time point of each FISH analysis. Bone marrow biopsies are not part of the study, but they are recommended to be performed every 6 to 12 months in the course of the disease. If a bone marrow biopsy is performed, conventional chromosome banding analyses on bone marrow metaphases and, additionally, FISH analyses of enriched CD34+ bone marrow cells and non-enriched bone marrow cells are performed. The results from peripheral blood are correlated with those of conventional banding and FISH analyses performed on bone marrow samples. The aims of this study are to detect acqired chromosomal aberrations in MDS patients from peripheral blood, to follow these anomalies by frequent analyses, to detect rare aberrations and to observe karyotype evolution from peripheral blood.

Study Type

Observational

Enrollment (Actual)

402

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Aachen, Germany
        • University Hospital Aachen
      • Dresden, Germany
        • University Hospital Dresden
      • Düsseldorf, Germany
        • University Hospital Düsseldorf
      • Frankfurt/Main, Germany
        • Onkologikum
      • Frankfurt/Main, Germany
        • University Hospital Frankfurt/Main
      • Goettingen, Germany
        • University Medical Center Göttingen
      • Goslar, Germany
        • Onkologische Kooperation Harz
      • Göttingen, Germany
        • Group Practice Meyer/Ammon/Müller
      • Magdeburg, Germany
        • Group Practice Uhle/Müller/Kröning/Jentsch-Ullrich
      • Munich, Germany
        • Technical University Munich
      • Munich, Germany
        • Group Practice Schmidt/Galler/Klapthor
      • Northeim, Germany
        • Group Practice Detken/Seraphin
      • Ulm, Germany
        • University Hospital Ulm

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

20 ml of peripheral blood (pb) of a MDS patient are enriched by immunomagnetic cell sorting (by MACS® system). A FISH analysis is performed on these CD34+ cells according to product protocols using the FISH probe panels described above. The percentage of aberrant interphase nuclei (IN) is measured related to all (at least 200) IN counted. FISH analyses are performed every 2 months in the 1st and every 3 months in the 2nd and 3rd year of follow-up by the same method using the standard panel and, if necessary, an informative probe of the super panel. Pb counts are documented once a month, and full blood counts with peripheral blasts are recommended at the time point of each FISH analysis. Bone marrow (bm) biopsies are not part of the study, but they are recommended to be performed every 6 to 12 months. If a bm biopsy is performed, conventional chromosome banding analyses on bm metaphases and FISH analyses of enriched CD34+ and non-enriched bm cells are performed.

Description

Inclusion Criteria:

  • Clinical diagnosis (cytomorphologic proof) of primary or secondary myelodysplastic syndrome (MDS) or
  • Suspected myelodysplastic syndrome (MDS).
  • Age > 18 years

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Screening and genetic monitoring of patients with MDS under different treatment modalities by cytogenetic analyses of circulating CD34+cells.
Time Frame: The first FISH analysis is performed at the time of study entry (initial screening) and after that every 2 months in the first year and every 3 months in the second and third year.
At each timepoint of FISH analysis the percentage of aberrant interphase nuclei is measured of all (at least 200) interphase nuclei counted.
The first FISH analysis is performed at the time of study entry (initial screening) and after that every 2 months in the first year and every 3 months in the second and third year.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut fuer anwendungsorientierte Forschung und klinische Studien GmbH

Collaborators

University Medical Center Goettingen

Investigators

  • Study Chair: Detlef Haase, MD, Prof., University Medical Center Göttingen

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 1, 2008

Primary Completion (Actual)

October 1, 2016

Study Completion (Actual)

October 1, 2019

Study Registration Dates

First Submitted

May 17, 2011

First Submitted That Met QC Criteria

May 17, 2011

First Posted (Estimate)

May 18, 2011

Study Record Updates

Last Update Posted (Actual)

February 21, 2020

Last Update Submitted That Met QC Criteria

February 20, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Diagnostik-Studie

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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