Hematopoietic Stem Cells Transplantation in Children With Combined Immunodeficiency (CID) (CD45RA)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02737384|
Recruitment Status : Terminated
First Posted : April 13, 2016
Last Update Posted : May 29, 2019
|Condition or disease||Intervention/treatment||Phase|
|Combined Immunodeficiencies||Biological: Depletion in CD45RA graft donor||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||4 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Hematopoietic Stem Cells Transplantation in Children With Combined Immunodeficiency (CID): Selective Depletion of Naive Cells From the Graft|
|Actual Study Start Date :||June 14, 2016|
|Actual Primary Completion Date :||October 26, 2017|
|Actual Study Completion Date :||October 26, 2017|
Biological: Depletion in CD45RA graft donor
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.
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
- Number of death [ Time Frame: 12 months after the transplantation ]
- Number of graft rejection [ Time Frame: 12 months after the transplantation ]
- Number of graft versus host disease (GVHD) grade III or IV [ Time Frame: 12 months after the transplantation ]
- Need of antiviral treatment [ Time Frame: 12 months after the transplantation ]to assess viral infection
- T Lymphocyte proliferations to phytohemagglutinin (PHA) [ Time Frame: 12 months after the transplantation ]to assess immune reconstitution
- Proportion of T CD4 and CD8 lymphocytes specific of cytomegalovirus, Epstein Barr virus and adenovirus [ Time Frame: 12 months after the transplantation ]to assess specific antiviral response
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02737384
|Hôpital Necker-Enfants Malades|
|Paris, France, 75015|
|Study Chair:||Marina CAVAZZANA, MD, PhD||Assistance Publique - Hôpitaux de Paris|