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| ID | Type | Description | Link |
|---|---|---|---|
| 2015-A01256-43 | Other Identifier | ANSM |
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| Name | Class |
|---|---|
| URC-CIC Paris Descartes Necker Cochin | OTHER |
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The purpose of this study is to evaluate selective depletion of naïve CD45RA+ T cells from allogenic peripheral blood stem cell graft in children transplanted for combined immune deficiency. The aims of this procedure are to prevent graft versus host disease (GVHD) while preserving anti-infectious response from donor memory T lymphocytes.
Combined immunodeficiencies (CIDs) are an heterogeneous group of primitive immunodeficiency (PID), which affect T cells development, function or both. These inherited conditions can only be cured by allogeneic hematopoietic stem cell transplantation (HSCT). These procedures have a high risk of morbidity and mortality such a graft versus host disease (GVHD), rejection of the graft and serious infections, especially in this population of children with PID. GVHD is more frequent and severe if the donor is not an identical sibling and/or presents an HLA-mismatch. GVHD requires high immunosuppression as prevention and treatment, and therefore impedes immunity against infections.
In vitro and animal models suggest that GVHD is mediated by naïve T cells. The aim of this study is to decrease the rate and severity of GVHD after selective depletion of naïve CD45RA+ T cells from allogeneic hematopoietic stem cell grafts in patients with CIDs with high risk of severe GVHD, and to preserve immunity against pathogens in a population with high vulnerability to infections.
The project aims is, first, to show improvement of rejection-free and GVH-free survival 12 months post-transplant, and secondly, to show the decrease of viral infection, and assess immune reconstitution kinetic and quality and specific antiviral responses, after a engraftment with naïve cell depleted allograft.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment | Experimental |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Depletion in CD45RA graft donor | Biological | Experimental treatment: negative fraction after CD34+ selection from PBSC graft is depleted of naïve CD45RA+ cells. this fraction is reinjected to the recipient and is the experimental product. Conditioning regimen: Up-front ATG from D-14 toD-11 Busulphan IV from D-8 to -5 Fludarabine from D-7 to D-4 Thiothepa D-3 to D-2 Graft: CD34+ cells positively selected cells from PBSC of the donor Post transplant immunosuppression: ciclosporin started at D-1 to D+100 |
| Measure | Description | Time Frame |
|---|---|---|
| Number of death | 12 months after the transplantation | |
| Number of graft rejection | 12 months after the transplantation | |
| Number of graft versus host disease (GVHD) grade III or IV | 12 months after the transplantation |
| Measure | Description | Time Frame |
|---|---|---|
| Need of antiviral treatment | to assess viral infection | 12 months after the transplantation |
| T Lymphocyte proliferations to phytohemagglutinin (PHA) | to assess immune reconstitution |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marina CAVAZZANA, MD, PhD | Assistance Publique - Hôpitaux de Paris | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hôpital Necker-Enfants Malades | Paris | Paris | 75015 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25282016 | Background | Touzot F, Neven B, Dal-Cortivo L, Gabrion A, Moshous D, Cros G, Chomton M, Luby JM, Terniaux B, Magalon J, Picard C, Blanche S, Fischer A, Cavazzana M. CD45RA depletion in HLA-mismatched allogeneic hematopoietic stem cell transplantation for primary combined immunodeficiency: A preliminary study. J Allergy Clin Immunol. 2015 May;135(5):1303-9.e1-3. doi: 10.1016/j.jaci.2014.08.019. Epub 2014 Oct 3. |
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| 12 months after the transplantation |
| Proportion of T CD4 and CD8 lymphocytes specific of cytomegalovirus, Epstein Barr virus and adenovirus | to assess specific antiviral response | 12 months after the transplantation |