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

NCT ID: NCT02737384

Last Updated: 2019-05-29

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 4 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-14
• Study Completion Date: 2017-10-26

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.

Conditions

Combined Immunodeficiencies

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Group Type: EXPERIMENTAL

Depletion in CD45RA graft donor

Intervention Type: 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

Interventions

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 12 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Marina CAVAZZANA, MD, PhD

Role: STUDY_CHAIR

Assistance Publique - Hôpitaux de Paris

Locations

Hôpital Necker-Enfants Malades

Paris, , France

Countries

France

References

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.

Reference Type: BACKGROUND

PMID: 25282016 (View on PubMed)

Other Identifiers

2015-A01256-43

Identifier Type: OTHER

Identifier Source: secondary_id

P140317

Identifier Type: -

Identifier Source: org_study_id