Transplant T CD4+ CCR7+ In Hematopoietic Stem Cells Allograft (CCR7-CD4-DPL)

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

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.

Study Overview

• Status: Completed
• Conditions: Acute Myeloblastic Leukemia
• Intervention / Treatment: Biological: blood

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 .

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • LIlle, France, 59037
    • Diseases of Blood Service HURIEZ hospital CHRU de LILLE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: receivers; 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; assessment pre-donation of hematopoietic stem cells (blood sample)
Experimental: Donors; 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; assessment pre-donation of hematopoietic stem cells (blood sample)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Investigators: Study Director: YAKOUB-AGHA IBRAHIM, Professor, CHRU de Lille

Study record dates

Study Major Dates

• Study Start (Actual): March 20, 2012
• Primary Completion (Actual): April 1, 2017
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: June 24, 2014
• First Submitted That Met QC Criteria: September 8, 2017
• First Posted (Actual): September 12, 2017

Study Record Updates

• Last Update Posted (Actual): September 12, 2017
• Last Update Submitted That Met QC Criteria: September 8, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Keywords: Hematopoietic Stem Cells; Lymphocytes CD4; Lymphocytes CCR7; ALLOGRAFT
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 2010_09; 2010-A01231-38 (Other Identifier: ID-RDB number, ANSM)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO