Interplay Between Immune and Metabolic Programs in Myelodysplastic Syndromes (IMET-MDS)

Interplay Between Immune and Metabolic Programs in Myelodysplastic Syndromes: Involvement in Leukemia Transformation and Therapeutic Targeting

Myelodysplastic syndromes (MDS) are a pre-leukemic condition with an extremely poor prognosis despite current treatments that justify new therapeutic approaches. Various studies have described the potential involvement of both immune compartment and cellular metabolism in the pathophysiology of MDS. The aim of this study is to determine the specific immune and metabolic profiles of the different classes of MDS and to identify predictive markers of progression/survival/response to therapy.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes

Detailed Description

Myelodysplastic syndromes (MDS) are a pre-leukemic condition with an extremely poor prognosis despite current treatments. It is the most frequent haematological disorder after the age of 65. Different approaches targeting the immune compartment have been developed but preliminary results seem to show variable response rates to these therapeutic highlighting the heterogeneity of MDS and the need to identify detailed immune profiles that are predictive of disease progression and can help in treatment choices. It therefore seems essential to complement the knowledge of immune profiles with an understanding of the metabolic profiles of MDS patients, as well as the links between these profiles and changes associated with progression and/or treatment resistance, in order to consider new therapeutic pathways.

Fresh samples from patients with MDS will be used to perform flow cytometry mapping of immune populations, T-cell and blast cell metabolism. Subsequently, a study of energy metabolism will be conducted using an extracellular flow analyzer and a sensitivity test for certain molecules targeting metabolic pathways. If possible, samples will be taken at different times during the course of treatment, according to the therapeutic protocols: diagnosis, progression/transformation, during azacitidine treatment.

• Study Type: Observational
• Enrollment (Estimated): 140

Contacts and Locations

• Study Contact: Name: Thibault Comont, MD, PhD; Phone Number: 0033 531156266; Email: comont.thibault@iuct-oncopole.fr

Study Locations

• France
  • Toulouse, France, 31500
    • Recruiting
    • IUCT-Oncopole University Hospital
    • Contact: Thibault Comont, MD, PhD; Phone Number: 0033 531156266; Email: comont.thibault@iuct-oncopole.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Patient with a myelodysplastic syndrome (WHO 2016 classification) of low risk (LR=IPSS-R<4.5) or high risk (HR=IPSS-R>4.5)

Description

Inclusion Criteria:

• Patients:

  • Patient over 18 years of age with a myelodysplastic syndrome (WHO 2016 classification) of low risk (LR=IPSS-R<4.5) or high risk (HR=IPSS-R>4.5);
  • Patient naïve to specific treatment of MDS;
  • Patient who expressed no opposition to participating in the study. ;
  • Patient affiliated with the social security system.

• Control:

  • over 18 years of age,
  • Sample from blood donation (regardless of age) Or Patient >60 years old, see at the geriatrics platform of the hospital la Grave (CHU of Toulouse),
  • having expressed his non opposition to participate in the study

Exclusion Criteria:

• Patients:

  • Myeloid disease other than MDS (including chronic myelomonocytic leukemia and MDS/SMP) ;
  • Ongoing treatments for MDS (excluding erythropoietin, granulocyte colony-stimulating factor and transfusions) ;
  • Medical conditions that may interfere with immune system testing: active cancer, active autoimmune disease, inflammatory conditions, immunosuppressive therapy. ; * Pregnant or breastfeeding women ; Patient's refusal ;
  • Person benefiting from a system of protection for adults (including guardianship, curators and safeguarding of justice)

• Control:

  • Medical conditions that may interfere with immune system testing: active cancer, active autoimmune disease, inflammatory conditions, immunosuppressive therapy. ; * Pregnant or breastfeeding women ;
  • Patient's refusal ;
  • Person benefiting from a system of protection for adults (including guardianship, curators and safeguarding of justice)

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Control patient; Healthy blood donor (regardless of age) Or Patient >60 years old, see at the geriatrics platform of the hospital la Grave (CHU of Toulouse), having expressed his non opposition to participate in the study
Patient with a myelodysplastic syndrome; Patient over 18 years of age with a myelodysplastic syndrome (WHO 2016 classification) of low risk (LR= International Prognostic Scoring System (IPSS)-R<4.5) or high risk (HR=Revised International Prognostic Scoring System>4.5)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immune and metabolic profiles will be evaluated by immunophenotyping	phenotypic study of one or more leukocyte sub-populations by flow cytometry	Day 0

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of time to progression/transformation and time to death	Clinical and biological data will be collected during follow up	Day 0 and through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: University Hospital, Toulouse
• Investigators: Principal Investigator: Thibault Comont, MD, PhD, University Hospital, Toulouse

Study record dates

Study Major Dates

• Study Start (Actual): February 23, 2021
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: March 11, 2021
• First Submitted That Met QC Criteria: March 16, 2021
• First Posted (Actual): March 18, 2021

Study Record Updates

• Last Update Posted (Actual): March 29, 2024
• Last Update Submitted That Met QC Criteria: March 28, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: metabolism; T-cells; Myelodysplastic syndromes
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia
• Other Study ID Numbers: RC31/20/0481

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No