Clinical trial NCT03280290: Transplant T CD4+ CCR7+ In Hematopoietic Stem Cells Allograft
Official title: Partial Selective Depletion in Lymphocytes Transplant T CD4+ CCR7+ in Hematopoeitic Stem Cells Allograft
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Myeloblastic Leukemia
Keywords: Lymphocytes CD4
Lymphocytes CCR7
ALLOGRAFT
Hematopoietic Stem Cells
Lead sponsor: University Hospital, Lille
Sponsor class: OTHER
First posted: 2017-09-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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 .

Eligibility criteria: 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.

Primary outcomes:
measure: Change the lymphocyte proliferation will be evaluated using a scintillation spectrometer
timeFrame: 1 day, 5 day ,8 day
measure: Change the functional properties of cells will be evaluated by T-SPOT TB®.
timeFrame: 1 day, 5 day ,8 day
Secondary outcomes:
measure: Response to anti-infectious immunity
timeFrame: 24 months
measure: Response to anti-tumor immunity
timeFrame: 24 months
Other outcomes:
Locations:
city: LIlle
country: France
facility: Diseases of Blood Service HURIEZ hospital CHRU de LILLE
Study officials:
affiliation: CHRU de Lille
name: YAKOUB-AGHA IBRAHIM, Professor
role: STUDY_DIRECTOR
References: