Hematopoietic Stem Cells Transplantation in Children With Combined Immunodeficiency (CID) (CD45RA)

May 24, 2019 updated by: Assistance Publique - Hôpitaux de Paris

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

4

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75015
        • Hôpital Necker-Enfants Malades

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of death
Time Frame: 12 months after the transplantation
12 months after the transplantation
Number of graft rejection
Time Frame: 12 months after the transplantation
12 months after the transplantation
Number of graft versus host disease (GVHD) grade III or IV
Time Frame: 12 months after the transplantation
12 months after the transplantation

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Need of antiviral treatment
Time Frame: 12 months after the transplantation
to assess viral infection
12 months after the transplantation
T Lymphocyte proliferations to phytohemagglutinin (PHA)
Time Frame: 12 months after the transplantation
to assess immune reconstitution
12 months after the transplantation
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
12 months after the transplantation

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 14, 2016

Primary Completion (ACTUAL)

October 26, 2017

Study Completion (ACTUAL)

October 26, 2017

Study Registration Dates

First Submitted

April 8, 2016

First Submitted That Met QC Criteria

April 8, 2016

First Posted (ESTIMATE)

April 13, 2016

Study Record Updates

Last Update Posted (ACTUAL)

May 29, 2019

Last Update Submitted That Met QC Criteria

May 24, 2019

Last Verified

April 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P140317
  • 2015-A01256-43 (OTHER: ANSM)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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