Sterile Inflammation and Molecular Aberrations in MDS

• Conditions: Myelodysplastic Syndromes
• Interventions: Diagnostic Test: Next Generation Sequencing; Diagnostic Test: Tumorimmunological examinations - multiplex assays/quantitative polymerase chain reaction; Diagnostic Test: flow cytometry; Diagnostic Test: Metagenomics of stool samples; Diagnostic Test: Clinical/demographic data; Other: Elicitation of the HRQoL

• Registration Number: NCT04313231
• Lead Sponsor: Medical University Innsbruck

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-01-22
• Study First Submitted: 2020-03-16
• Study First Submitted QC: 2020-03-16
• Study First Posted: 2020-03-18
• Status Verified: 2022-01
• Last Update Submitted: 2022-04-06
• Last Update Posted: 2022-04-07
• Primary Completion: 2023-01
• Study Completion: 2023-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 130

Inclusion Criteria

• 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

Exclusion Criteria

• 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
• Steroid therapy (>10mg Prednison/day or equivalent), regardless of its necessity up to 4 weeks before inclusion in the study
• 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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
MDS	Next Generation Sequencing	* 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)
control	Metagenomics of stool samples	age-matched healthy persons
control	Clinical/demographic data	age-matched healthy persons
MDS	Tumorimmunological examinations - multiplex assays/quantitative polymerase chain reaction	* 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)
MDS	flow cytometry	* 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)
control	Elicitation of the HRQoL	age-matched healthy persons
MDS	Elicitation of the HRQoL	* 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)
control	Tumorimmunological examinations - multiplex assays/quantitative polymerase chain reaction	age-matched healthy persons
control	flow cytometry	age-matched healthy persons
MDS	Metagenomics of stool samples	* 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)
MDS	Clinical/demographic data	* 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)
control	Next Generation Sequencing	age-matched healthy persons

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Medical University of Innsbruck; 🇦🇹 Innsbruck, Tyrol, Austria