Hematopoietic Stem Cells Transplantation in Children With Combined Immunodeficiency (CID)

Combined Immunodeficiencies Clinical Trial

— CD45RA  

Official title:

Hematopoietic Stem Cells Transplantation in Children With Combined Immunodeficiency (CID): Selective Depletion of Naive Cells From the Graft

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02737384
• Other study ID #: P140317
• Secondary ID: 2015-A01256-43
• Status: Terminated
• Phase: Phase 2
• Start date: June 14, 2016
• Est. completion date: October 26, 2017

Study information

• Verified date: April 2019
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: October 26, 2017
• Est. primary completion date: October 26, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months to 18 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Combined Immunodeficiencies
• Immunologic Deficiency Syndromes

Intervention

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. 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

Locations

Country	Name	City	State
France	Hôpital Necker-Enfants Malades	Paris

Sponsors (1)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris

Country where clinical trial is conducted

France, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of death		12 months after the transplantation
Primary	Number of graft rejection		12 months after the transplantation
Primary	Number of graft versus host disease (GVHD) grade III or IV		12 months after the transplantation
Secondary	Need of antiviral treatment	to assess viral infection	12 months after the transplantation
Secondary	T Lymphocyte proliferations to phytohemagglutinin (PHA)	to assess immune reconstitution	12 months after the transplantation
Secondary	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