Transplant T CD4+ CCR7+ In Hematopoietic Stem Cells Allograft

Study Overview
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Brief Summary
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This is a preclinical study prior to the establishment of a cell therapy protocol applicable to humans. The main objective is to evaluate the decrease in alloreactivity of TCD4 + population by partial selective depletion of CD4 + CCR7 + graft to less than 50 % of CD4 + totals. To test the alloreactivity of donor T lymphocytes.

Detailed Description
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This is a preclinical study prior to the establishment of a cell therapy protocol applicable to humans. The main objective is to evaluate the decrease in alloreactivity of TCD4 + population by partial selective depletion of CD4 + CCR7 + graft to less than 50 % of CD4 + totals. To test the alloreactivity of donor T lymphocytes , T lymphocytes CD4 + CCR7 + donor will be stimulated by mature dendritic cells (DC) derived from recipient circulating monocytes in a mixed lymphocyte reaction model sensitized ( MLDCR ) , experiencing HLA -compatibility . This first step will confirm the results previously obtained in a situation incompatible HLA .

Official Title
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Partial Selective Depletion in Lymphocytes Transplant T CD4+ CCR7+ in Hematopoeitic Stem Cells Allograft

Conditions
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Acute Myeloblastic Leukemia

Intervention / Treatment
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* Biological: blood


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria of the receiver anti -infectious immunity Man or woman aged 18-65 years Eligible for allo - HSCs from peripheral blood stem cells from a compatible donor HLA family (Annex 3 , the pre- transplant assessment must be enabled) In a complete remission rate of leucocytes with ≥ 2G / L Affiliated to social security person or beneficiary of such a scheme. Having signed informed consent Inclusion criteria for the study of the receiver of anti tumor immunity Man or woman aged 18-65 years Achieved a hyperleucocytic acute myelogenous leukemia ( leukocytes ≥ 20G / L) Patients whose blasts at diagnosis were cryopreserved in the tumor bank of the University Hospital of Lille (Professor Claude Prudhomme ) Eligible for allo - HSCs from peripheral blood stem cells from a compatible donor HLA family (Annex 3 , the pre- transplant assessment must be enabled) In a complete remission rate of leucocytes with ≥ 2G / L Affiliated to social security person or beneficiary of such a scheme. Having signed informed consent receivers Inclusion criteria of the donor Man or woman aged 18-65 years Member of the HLA-matched siblings and A, B, Cw, DR, DQ Eligible to donate peripheral blood stem cells for allo-HSCs (Appendix 2, pre donation assessment must be enabled) Having a rate of circulating lymphocytes ≥ 1 G / L Having a proportion of CD4 + CCR7 + ≥ 80% of the total CD4 T population The statutes CMV and EBV are known (positive or negative). Affiliated to social security person or beneficiary of such a scheme. who signed informed consent - Exclusion Criteria: Criteria for non inclusion of the pairs donor / Receiver Private person of liberty by judicial or administrative decision Person subject to a measure of legal protection Pregnant or breastfeeding woman People do not understand French or understanding with a disability. Major Protected Person in emergency and refusing or unable to give informed consent At any time, individuals may request to be removed from the study Each subject may come out of the study by decision of the competent administrative authority of the promoter and the coordinating investigator but also by decision of a co-investigator or by decision of the interested himself in accordance with regulations and as mentioned in the form of obtaining consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: receivers<br>Eligible for allo-HSCs from peripheral blood stem cells from a compatible donor HLA family (Appendix 1, the pre-transplant assessment must be enabled) In a complete remission rate of leucocytes with ≥ 2G / L Affiliated to social security person or beneficiary of such a scheme. | Biological: blood<br>* assessment pre-donation of hematopoietic stem cells (blood sample)<br>|
| Experimental: Donors<br>Member of the siblings and HLA-matched A, B, Cw, DR, DQ Eligible to donate peripheral blood stem cells for allo-HSCs (Appendix 2, pre donation assessment must be enabled) Having a rate of circulating lymphocytes ≥ 1 G / L Having a proportion of CD4 + CCR7 + ≥ 80% of the total CD4 T population The statutes CMV and EBV are known (positive or negative). Affiliated to social security person or beneficiary | Biological: blood<br>* assessment pre-donation of hematopoietic stem cells (blood sample)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change the lymphocyte proliferation will be evaluated using a scintillation spectrometer | Decrease in alloreactivity of TCD4.(composite) Decrease population by partial selective depletion of CD4 + CCR7 + graft to less than 50% of total CD4 +will be evaluated on this basis criteria. | 1 day, 5 day ,8 day | 
| Change the functional properties of cells will be evaluated by T-SPOT TB®. | Decrease in alloreactivity of TCD4.(composite) Decrease population by partial selective depletion of CD4 + CCR7 + graft to less than 50% of total CD4 +will be evaluated on this basis criteria. | 1 day, 5 day ,8 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to anti-infectious immunity | Measure the anti-infectious immunity during a partial selective depletion of TCD4 + CCR7 + (≤ 50%) | 24 months | 
| Response to anti-tumor immunity | Measure the anti-tumor immunity during a partial selective depletion of TCD4 + CCR7 + (≤ 50%) | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lymphocytes CD4, Lymphocytes CCR7, ALLOGRAFT, Hematopoietic Stem Cells