Study of an Innovative Therapy Using CAR-T Cells Targeting IL-1RAP in Patients With High-Risk Myelodysplastic Syndromes (MDS

NCT07455500 | Not Yet Recruiting DMC

• 1 other identifier: 38RC25.0260
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

The surface protein IL-1RAP, expressed by leukemic blast cells, represents a target of interest for patients with acute myeloid leukemia (AML). Its restricted and specific expression on leukemic cells makes it a promising target for chimeric antigen receptor T-cell (CAR-T cell) immunotherapy. High-risk myelodysplastic syndromes (MDS) correspond to a pre-leukemic condition characterized by an accumulation of bone marrow blasts. Unfortunately, very few effective treatments are currently available, apart from allogeneic hematopoietic stem cell transplantation, which can only be performed in a limited number of patients. It has been demonstrated that high-risk MDS blasts express IL-1RAP. The project will aim to:

• Confirm IL-1RAP expression on primary MDS blast cells.
• Measure circulating soluble IL-1RAP in plasma samples from MDS patients.
• Investigate the interaction with the microenvironment in relation to IL-1RAP cellular expression.
• Evaluate the effect of first-line standard treatment for MDS on IL-1RAP surface expression.
• Assess the in vitro efficacy of an IL-1RAP-targeted CAR-T cell on MDS leukemic stem cells.
• Assess the in vivo efficacy of an IL-1RAP-targeted CAR-T cell in a humanized murine model of MDS. To successfully conduct this project, it is essential to collect blood and bone marrow samples from high-risk MDS patients This project will require the collection of bone marrow and blood samples from patients with MDS, either newly diagnosed or currently undergoing treatment.

Conditions

Myelodysplastic Syndrome

Keywords

IL-1RAP; CAR-T cells

Outcome Measures

Primary Outcomes (1)

• Validation of IL-1RAP CAR-T Cell Efficacy:

  In vitro: Co-culture of CD34⁺ hematopoietic stem cells from high-risk MDS patients with IL-1RAP CAR-T cells: 1) to assess cytotoxicity (% of cell death), 2) including measurement of IFN-γ, TNF, granzyme, and perforin secretion. In vivo: Evaluation of the therapeutic effect of IL-1RAP CAR-T cells in a murine xenograft model using CD34⁺ MDS HSCs previously engineered to express the luciferase gene, with therapeutic efficacy assessed by reduction in bioluminescence (%).

  Baseline through study completion, an average of 1 year

Study Arms (1)

MDS patients with low and high risk MDS

EXPERIMENTAL

Other: Bone marrow and blood sampling

Interventions

Bone marrow and blood sampling OTHER

Patients diagnosed with, or suspected of having, low-risk or high-risk myelodysplastic syndrome (MDS) will undergo bone marrow aspirate and peripheral blood sample collection at the time of initial diagnostic evaluation. These procedures will be performed exclusively within the context of routine clinical care, without any additional invasive procedures specifically for research purposes. For patients with high-risk MDS, additional bone marrow and peripheral blood samples may be collected in the event of suspected relapse during active treatment or following allogeneic hematopoietic stem cell transplantation, in accordance with standard-of-care clinical assessments

MDS patients with low and high risk MDS

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient with Myelodysplastic Syndrome (MDS)
• Low-risk MDS according to the IPSS-M (20).
• MDS confirmed by bone marrow cytology with a blast percentage between 5% and 19% and/or associated with cytogenetic abnormalities or gene mutations indicating poor prognosis.
• High-risk MDS according to the IPSS-M
• At diagnosis or in cases of relapse/refractoriness to hypomethylating agents or to allogeneic hematopoietic stem cell transplantation.

You may not qualify if:

• Patient not diagnosed with MDS or patient diagnosed with acute myeloid leukemia.
• Patient with an active solid tumor or another active hematologic malignancy requiring treatment.
• Patient with a contraindication to performing bone marrow aspiration.
• Individuals referred to in Articles L1121-6 to L1121-8 of the French Public Health Code

Sponsors & Collaborators

• University Hospital, Grenoble: lead

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Mathieu Meunier, MD, PhD

  CHU Grenoble Alpes

  STUDY DIRECTOR

Central Study Contacts

Mathieu Meunier, MD, PhD

CONTACT

476768601; mmeunier2@chu-grenoble.fr

Sophie Park, MD, PhD

CONTACT

spark@chu-grenoble.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: March 6, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2031
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share