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Immunoevasive Tactics Employed by Myeloid Malignancy After Allogeneic Stem Cell Transplantation

Study of the Immunoevasive Mecanisms and Especially Myeloid Suppressive Cells in the Medullar Microenvironment Employed by Myeloid Malignancy (AML and High Risk MDS) When Relapsing After Allogeneic Stem Cell Transplantation

Status
UNKNOWN
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03964922
Acronym
EVADE
Enrollment
104
Registered
2019-05-28
Start date
2019-09-01
Completion date
2022-11-01
Last updated
2019-05-28

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Allogeneic Stem Cell Transplantation, Immune Evasion, Tumor, Relapse Leukemia

Brief summary

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is still the only treatment available to cure acute myeloid leukemia and high risk myelodysplasia. Allo-HSCT has an anti-tumor effect (called the graft versus leukemia effect= GVL) mediated by donor lymphocytes. This GVL effect is often associated with graft-versus-host disease (GVHD). Several studies have shown that the relapse incidence is lower in patients developing chronic GVHD. These studies confirm the impact of donor immune system on leukemic residual cells. In fact, the relapse incidence increased in patients with no sign of GVHD. The investigators assume that leukemic cells probably use mechanisms to inhibit the allogeneic response. These escape mechanisms to immunosurveillance have been described in other malignancies. Out of context of the allo-HSCT, in acute myeloid leukemias and myelodysplasia, correlations between the severity of the disease and the presence of regulatory T cells (Tregs) or exhausted T cells (PD1 positive) in the bone marrow and in the blood of patients were described at the time of diagnosis or relapse. Myeloid Derived Suppressive Cells (MDSCs) have been described as capable of inducing Tregs and exhausted T cells in the tumor microenvironment.The investigators want to evaluate the role of myeloid suppressive cells in bone marrow after allo HSCT. They hypothesize that their presence in bone marrow and / or blood recipient is correlated to the relapse incidence.

Interventions

BIOLOGICALblood sample

20 ml at inclusion, and 20ml at 1, 3, 6 and 12 months after allo HSCT

3 ml at inclusion, and 3 ml at 1, 3, 6 and 12 months after allo HSCT

Sponsors

Central Hospital, Nancy, France
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to 71 Years
Healthy volunteers
No

Inclusion criteria

* Patients with acute myeloid leukemia in complete cytological remission with intermediate or high risk prognosis according to ELN 2017 * Patients with myelodysplasia according to the WHO 2016 definition, with IPSS ≥1.5 and disease status is : stable or in partial response or complete response according to IWG 2006. * Patients with indication of first allo-HSCT with a matched related or unrelated donor * Patients receiving non-myeloablative or reduced toxicity conditioning * Patients affiliated to a social security scheme * Patients who have received a complete information on the organization of the research and signed his informed consent

Exclusion criteria

* Patients with an alternative donor (HLA 5/10 or unit cord blood) * Patients with another active cancer or a history of cancer diagnosed in the previous 5 years * Patients with uncontrolled infection at the time of inclusion, or with positive HIV (1 + 2) or HTLV (1 + 2), Hepatitis C or active hepatitis B * Patients referred to in Articles L. 1121-5, L. 1121-7 and L1121-8 of the Public Health Code.

Design outcomes

Primary

MeasureTime frameDescription
Myeloid suppressive cells and relapse incidence2 yearsTo investigate the relationship between the percentage of myeloid derived suppressive cells (MDSCs) in total leukocytes in peripheral blood and the relapse incidence after allogeneic stem cell transplantation. The patients will be grouped according to median MDSC frequency values. Relapse incidence will be compared across the two groups (low and high frequency of MDSC).

Secondary

MeasureTime frameDescription
Myeloid suppressive cells and the medullar microenvironment (regulatory T cells and mesenchymal stem cells)2 yearsTo correlate levels of bone marrow MDSC and regulatory T cells (Tregs) and exhausted T cells and the quality of mesenchymal cells in bone marrow.
percentage of myeloid suppressive cells2 years
incidence of acute GVHD2 years
incidence of chronic GVHD2 years

Contacts

Primary ContactMaud D'AVENI, MD
m.daveni-piney@chru-nancy.fr+33383153289
Backup ContactMarie-Therese RUBIO, MD
m.rubio@chru-nancy.fr+33383153282

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 8, 2026