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

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ClinicalTrials.gov Identifier: NCT02737384
Recruitment Status : Terminated
First Posted : April 13, 2016
Last Update Posted : May 29, 2019
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Combined Immunodeficiencies Biological: Depletion in CD45RA graft donor Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

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





Primary Outcome Measures :
  1. Number of death [ Time Frame: 12 months after the transplantation ]
  2. Number of graft rejection [ Time Frame: 12 months after the transplantation ]
  3. Number of graft versus host disease (GVHD) grade III or IV [ Time Frame: 12 months after the transplantation ]

Secondary Outcome Measures :
  1. Need of antiviral treatment [ Time Frame: 12 months after the transplantation ]
    to assess viral infection

  2. T Lymphocyte proliferations to phytohemagglutinin (PHA) [ Time Frame: 12 months after the transplantation ]
    to assess immune reconstitution

  3. 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



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Ages Eligible for Study:   12 Months to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Locations
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France
Hôpital Necker-Enfants Malades
Paris, France, 75015
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
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Study Chair: Marina CAVAZZANA, MD, PhD Assistance Publique - Hôpitaux de Paris

Publications:
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT02737384     History of Changes
Other Study ID Numbers: P140317
2015-A01256-43 ( Other Identifier: ANSM )
First Posted: April 13, 2016    Key Record Dates
Last Update Posted: May 29, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
Combined immunodeficiencies
hematopoietic stem cell transplantation
CD45RA
primitive immunodeficiencies
pediatric transplantation
CD45RA depletion
Additional relevant MeSH terms:
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Immunologic Deficiency Syndromes
Immune System Diseases