NCT04313231

Brief Summary

The objective of this study is the description of the possible association between genetic mutation/aberration profiles, inflammatory tonus and clinical phenotype based on PROMs and HRQoL. Apart from gaining a better understanding of the causal correlation between genetics, sterile inflammatory processes and QoL (e.g. fatigue) in MDS, this study is supposed to identify potential novel biomarkers and, ultimately, therapeutic targets.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
130

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Jan 2020

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 22, 2020

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

March 16, 2020

Completed
2 days until next milestone

First Posted

Study publicly available on registry

March 18, 2020

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2023

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2023

Completed
Last Updated

April 7, 2022

Status Verified

January 1, 2022

Enrollment Period

2.9 years

First QC Date

March 16, 2020

Last Update Submit

April 6, 2022

Conditions

Myelodysplastic Syndromes

Keywords

anemiahealth-related quality of lifeinflammation

Outcome Measures

Primary Outcomes (2)

  • Definition of correlation between molecular aberrations and the sterile inflammatory tonus

    baseline

  • 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

    baseline

Secondary Outcomes (1)

  • Definition of correlation of sterile inflammatory tonus with clinical variables (e.g. progression to secondary acute myeloid leukemia (sAML), complications (e.g. infections), and survival)

    baseline

Study Arms (2)

MDS

* Female and male patients aged 18 years and older * MDS, MDS/MPN diagnosis based on current WHO classification. CCUS and CHIP defined by Valent (Valent, Oncotarget, 2018) and by Stauder (Stauder, Blood, 2018)

Diagnostic Test: Next Generation SequencingDiagnostic Test: Tumorimmunological examinations - multiplex assays/quantitative polymerase chain reactionDiagnostic Test: flow cytometryDiagnostic Test: Metagenomics of stool samplesDiagnostic Test: Clinical/demographic dataOther: Elicitation of the HRQoL

control

age-matched healthy persons

Diagnostic Test: Next Generation SequencingDiagnostic Test: Tumorimmunological examinations - multiplex assays/quantitative polymerase chain reactionDiagnostic Test: flow cytometryDiagnostic Test: Metagenomics of stool samplesDiagnostic Test: Clinical/demographic dataOther: Elicitation of the HRQoL

Interventions

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%.

MDScontrol
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.

MDScontrol
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.

MDScontrol
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).

MDScontrol
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).

MDScontrol
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.

MDScontrol

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodProbability Sample
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)

You may qualify if:

  • Female and male patients \> 18 years
  • MDS, MDS/MPN diagnosis based on current WHO classification. CCUS and CHIP defined by Valent (Valent, Oncotarget, 2018) and by Stauder (Stauder, Blood, 2018)
  • Signed and dated declaration of consent by the patient according to ICH-GCP Guidelines

You may not qualify if:

  • Any other illness, whether physical or mental, or any laboratory abnormalities which prevent a declaration of consent by the patient
  • Patients with an acute and/or uncontrolled infection, including patients that are afebrile under treatment with antibiotic/antifungal/antiviral prophylactic medication
  • Any pre-existing autoimmune disease requiring a systemic immunosuppression
  • Anamnestic and/or current therapy with hypomethylating agents (HMA) or immunomodulatory imide drugs (IMiDs)
  • Status post allogenic stem cell transplantation
  • Previous or ongoing chemotherapy
  • Pregnancy or breastfeeding period

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Medical University of Innsbruck

Innsbruck, Tyrol, 6020, Austria

RECRUITING

Related Publications (3)

  • Valent P, Stauder R, Theurl I, Geissler K, Sliwa T, Sperr WR, Bettelheim P, Sill H, Pfeilstocker M. Diagnosis, management and response criteria of iron overload in myelodysplastic syndromes (MDS): updated recommendations of the Austrian MDS platform. Expert Rev Hematol. 2018 Feb;11(2):109-116. doi: 10.1080/17474086.2018.1420473. Epub 2018 Jan 2.

    PMID: 29292655BACKGROUND

  • Stauder R, Valent P, Theurl I. Anemia at older age: etiologies, clinical implications, and management. Blood. 2018 Feb 1;131(5):505-514. doi: 10.1182/blood-2017-07-746446. Epub 2017 Nov 15.

    PMID: 29141943BACKGROUND

  • Loacker L, Petzer V, Bachmann S, Griesmacher A, Wolf D, Stauder R. High concordance of clone detection between peripheral blood and bone marrow by targeted next-generation sequencing-A pilot study in patients with MDS. Br J Haematol. 2023 Aug;202(3):e16-e19. doi: 10.1111/bjh.18889. Epub 2023 Jun 1. No abstract available.

    PMID: 37263977DERIVED

MeSH Terms

Conditions

Myelodysplastic SyndromesAnemiaInflammation

Interventions

Flow Cytometry

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cell SeparationCytological TechniquesClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisCytophotometryFluorometryLuminescent MeasurementsPhotometryChemistry Techniques, AnalyticalInvestigative Techniques

Study Officials

  • Domink Wolf, Univ.Prof.

    Medical University Innsbruck

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Domink Wolf, Univ.Prof.

CONTACT

0043512504dominik.wolf@i-med.ac.at

Verena Petzer, MD

CONTACT

0043512504

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Target Duration
12 Months
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 16, 2020

First Posted

March 18, 2020

Study Start

January 22, 2020

Primary Completion

January 1, 2023

Study Completion

January 1, 2023

Last Updated

April 7, 2022

Record last verified: 2022-01

Locations

AU(1)