Sterile Inflammation and Molecular Aberrations in MDS

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 18 years and older
• All sexes
• Healthy volunteers accepted
• Adult, Older adult

Study population: MDS, MDS/MPN diagnosis based on current WHO classification. CCUS and CHIP defined by Valent (Valent, Oncotarget, 2018) and by Stauder (Stauder, Blood, 2018)

Trial locations and contacts

1 site in 1 country.

About this study

Official title: Sterile Inflammation and Molecular Aberrations in Myelodysplastic Syndrome: Determinants of Quality of Life and Vulnerability

Conditions

Myelodysplastic Syndromes

Being tested

Next Generation Sequencing, Tumorimmunological examinations - multiplex assays/quantitative polymerase chain reaction, flow cytometry, Metagenomics of stool samples, Clinical/demographic data

Keywords

anemia, health-related quality of life, inflammation

Medical subject headings

Myelodysplastic Syndromes, Anemia, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• Next Generation SequencingDiagnostic test

  Sequencing of patient samples will be performed in the facilities of ZIMCL. Following DNA extraction, the sequencing of granulocytes as well as of lymphocytes (control) will be carried out. IN addition to whole exome sequencing, a panel from SOPHIA GENETICS (which is also available for routine diagnostics) will be applied including the following MDS specific genes: ASXL1, BRAF, CBL, CEBPA, CSF3R, DNMT3A, EZH2, FLT3, HRAS, IDH1, IDH2, KRAS, MPL, NPM1, NRAS, RUNX1, SF3B1, SRSF2, TET2, TP53, U2AF1, WT1, ZRSR. Each patient sample will be "bulk sequenced", meaning that relevant mutations are detected down to an allele frequency of 2%.

• Tumorimmunological examinations - multiplex assays/quantitative polymerase chain reactionDiagnostic test

  Inflammasome activation is quantified by analyses of inflammasome-associated cytokine patterns. Multiplex assays for the quantification of the inflammasome-specific cytokines will be done from serum as well as from supernatants the stimulated blood cells. Cytokine quantification is carried out with Luminex FlexMap 3D. Serum cytokine levels will be quantitated in parallel.

  Quantification of RNA expression levels of inflammasome-related gene products will be performed by qPCRs from unstimulated and stimulated (=cryotube) blood cells. The necessary RNA extraction will be performed using a RNA extraction kit.

• flow cytometryDiagnostic test

  A detailed evaluation of the individual immune status is being conducted by the analysis of two specialized panels: Panel A provides a broad overview over various immune cell populations, while Panel B identifies T-cell sup-populations.

• Metagenomics of stool samplesDiagnostic test

  DNA will be extracted from frozen fecal samples applying a bead-beating method using a GNOME DNA Isolation Kit (MP Biomedicals). DNA quality will be assessed using an Agilent 4200 TapeStation (Agilent Technologies). After final precipitation, DNA samples will be re-suspended in TE buffer and stored at -80 °C for further sequencing analysis. To this end, sequencing libraries will be generated using a Nextera XT DNA Sample Prep Kit (Illumina). Library quality will be confirmed using an Agilent 4200 TapeStation. Whole-genome shotgun sequencing of fecal samples will be carried out on a HiSeq2500 platform (Illumina).

• Clinical/demographic dataDiagnostic test

  Demographic and clinical data include: age, age at initial diagnosis, sex, diagnosis, actual comorbidities, medication at inclusion in study, cytogenetic and molecular profiles and standard laboratory parameters (blood count, differential leukocyte count, biochemistry, iron status, inflammatory markers like CRP, albumin, fibrinogen).

• Elicitation of the HRQoLOther

  Evaluation of HRQOL, of functional activities and of performance status will be done by the patient and/or the physician using validated scores.

What is being measured

The primary outcome is the main question the study is designed to answer.

1. Definition of correlation between molecular aberrations and the sterile inflammatory tonus

   Measured: baseline

2. Definition how genetic aberrations and associated sterile inflammation impacts on health-related quality of life (HRQoL, e.g. fatigue) and functional activities in patients with MDS, MDS/MPN, or CHIP/CCUS

   Measured: baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted18 Mar 2020
2. Study start22 Jan 2020
3. Primary completionJan 2023 (estimated)
4. Study completionJan 2023 (estimated)

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Publications (3)Papers the sponsor has linked to this study.
• Other trials for Myelodysplastic SyndromesStudies of the same condition, open and under way.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.