Immunoevasive Tactics Employed by Myeloid Malignancy After Allogeneic Stem Cell Transplantation

Allogeneic Stem Cell Transplantation Clinical Trial

— EVADE  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT03964922
• Other study ID #: 2019-A00842-55
• Status: Not yet recruiting
• Phase: N/A
• Start date: September 1, 2019
• Est. completion date: November 1, 2022

Study information

• Verified date: May 2019
• Source: Central Hospital, Nancy, France
• Contact: Maud D'AVENI, MD
• Phone: +33383153289
• Email: m.daveni-piney[@]chru-nancy.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 104
• Est. completion date: November 1, 2022
• Est. primary completion date: June 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 71 Years

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Biological:
• blood sample
20 ml at inclusion, and 20ml at 1, 3, 6 and 12 months after allo HSCT
• bone marrow sample
3 ml at inclusion, and 3 ml at 1, 3, 6 and 12 months after allo HSCT

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Central Hospital, Nancy, France

References & Publications (4)

D'Aveni M, Rossignol J, Coman T, Sivakumaran S, Henderson S, Manzo T, Santos e Sousa P, Bruneau J, Fouquet G, Zavala F, Alegria-Prévot O, Garfa-Traoré M, Suarez F, Trebeden-Nègre H, Mohty M, Bennett CL, Chakraverty R, Hermine O, Rubio MT. G-CSF mobilizes CD34+ regulatory monocytes that inhibit graft-versus-host disease. Sci Transl Med. 2015 Apr 1;7(281):281ra42. doi: 10.1126/scitranslmed.3010435. — View Citation

Kong Y, Zhang J, Claxton DF, Ehmann WC, Rybka WB, Zhu L, Zeng H, Schell TD, Zheng H. PD-1(hi)TIM-3(+) T cells associate with and predict leukemia relapse in AML patients post allogeneic stem cell transplantation. Blood Cancer J. 2015 Jul 31;5:e330. doi: 10.1038/bcj.2015.58. — View Citation

Kumar B, Garcia M, Weng L, Jung X, Murakami JL, Hu X, McDonald T, Lin A, Kumar AR, DiGiusto DL, Stein AS, Pullarkat VA, Hui SK, Carlesso N, Kuo YH, Bhatia R, Marcucci G, Chen CC. Acute myeloid leukemia transforms the bone marrow niche into a leukemia-permissive microenvironment through exosome secretion. Leukemia. 2018 Mar;32(3):575-587. doi: 10.1038/leu.2017.259. Epub 2017 Aug 17. — View Citation

Nadal E, Garin M, Kaeda J, Apperley J, Lechler R, Dazzi F. Increased frequencies of CD4(+)CD25(high) T(regs) correlate with disease relapse after allogeneic stem cell transplantation for chronic myeloid leukemia. Leukemia. 2007 Mar;21(3):472-9. Epub 2007 Jan 11. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Myeloid suppressive cells and relapse incidence	To 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).	2 years
Secondary	Myeloid suppressive cells and the medullar microenvironment (regulatory T cells and mesenchymal stem cells)	To correlate levels of bone marrow MDSC and regulatory T cells (Tregs) and exhausted T cells and the quality of mesenchymal cells in bone marrow.	2 years
Secondary	percentage of myeloid suppressive cells		2 years
Secondary	incidence of acute GVHD		2 years
Secondary	incidence of chronic GVHD		2 years