Hematopoietic Stem Cells Transplantation in Children With Combined Immunodeficiency (CID)
- Conditions
- Combined Immunodeficiencies
- Interventions
- Biological: Depletion in CD45RA graft donor
- Registration Number
- NCT02737384
- Lead Sponsor
- Assistance Publique - Hôpitaux de Paris
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 4
- Patient from 12 months to 18 years
- Combined immunodeficiencies with known molecular diagnosis or if unknown, corresponding of p-CID study's definition
- Hematopoietic stem cell Transplantation planned with one of the following donors :
- sibling with 1 or 2 HLA antigens mismatch
- parent 10/10 or 9/10 identical
- unrelated donor: 10/10 or 9/10 identical
- Consent form signed by the child's legal guardian
- Patient using effectiveness contraception during this trial
- Affiliated or beneficiary of a health insurance regimen
- Wiskott-Aldrich syndrome
- Ongoing pregnancy
- Positive HIV PCR
- Contraindication for hematopoetic stem cell transplantation
- Geno-identical donor in the siblings
- hematopoetic stem cell transplantation antecedent
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Treatment Depletion in CD45RA graft donor -
- Primary Outcome Measures
Name Time Method 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 Number of death 12 months after the transplantation
- Secondary Outcome Measures
Name Time Method T Lymphocyte proliferations to phytohemagglutinin (PHA) 12 months after the transplantation to assess immune reconstitution
Need of antiviral treatment 12 months after the transplantation to assess viral infection
Proportion of T CD4 and CD8 lymphocytes specific of cytomegalovirus, Epstein Barr virus and adenovirus 12 months after the transplantation to assess specific antiviral response
Trial Locations
- Locations (1)
Hôpital Necker-Enfants Malades
🇫🇷Paris, France