Gene Therapy for X-linked Severe Combined Immunodeficiency

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Brief Title

Gene Therapy for X-linked Severe Combined Immunodeficiency

Official Title

Protocol No. 2 of Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1) Using a Self Retroviral Vector - SCID2

Brief Summary

      X-linked severe combined immunodeficiency (SCID-X1) is an inherited disorder that results in
      failure of development of the immune system in boys. This trial aims to treat SCID-X1
      patients using gene therapy to replace the defective gene.

Detailed Description

      The objective of this protocol is to reinitiate an ex vivo gene therapy clinical protocol to
      treat patients with SCID-X1 without HLA identical family donor nor HLA identical unrelated
      donor (bone marrow and cord blood) available in an adequate time with the clinical conditions
      of the patient at diagnosis (approximately 6 weeks). This clinical protocol No. 2 of SCID-X1
      must be as efficient than the previous one but must involve a risk of insertional mutagenesis
      significantly reduced as compared to the first protocol.

      The main purpose of the study is the study of toxicity: tolerance and incidence of serious
      adverse effects.

      Secondary goals are the evaluation of immune reconstitution allowing the cure of infections
      present at the time of gene therapy, assessment of integration sites, and finally the
      long-term correction of immunosuppression.

        1. safety assessment : clinical effects, possible emergence of clonal lymphocyte
           proliferation, potential activation of proto-oncogene;

        2. efficacy assessment of ex vivo transduction of CD34 + hematopoietic stem cells of the
           patient through the use of retroviral vector pSRS11.EFS.IL2RG.pre;

        3. assessment of immune reconstitution : phenotype, number and function of different T, NK
           and B cells subpopulations;

        4. longitudinal evaluation of clinical effects in terms of improvement or complete
           restoration of immunity;

        5. biological efficacy assessment of this new vector SIN, assessment of molecular
           characteristics of retroviral integration.

Study Phase

Phase 1/Phase 2

Study Type


Primary Outcome

Assessment of immunological reconstitution at short term

Secondary Outcome

 Molecular characterization of gene transfer


X-linked Severe Combined Immunodeficiency


Gene transfer

Study Arms / Comparison Groups

Description:  Gene transfer


* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information

Recruitment Status


Estimated Enrollment


Start Date

December 2010

Completion Date

October 2016

Primary Completion Date

July 2015

Eligibility Criteria

        Inclusion criteria :

          -  Boys diagnosed during the first year of life

          -  Diagnosis of classical SCID-X1 based on immunophenotype (absent, or reduced numbers of
             non-functional T lymphocytes) and confirmed by DNA sequencing

          -  No HLA identical family donor and no HLA identical unrelated donor (10/10 antigens)
             found in the 6 weeks following the beginning of the search. This period could be
             shortened if the probability to find a donor is low or if the clinical situation
             (gravity) required

          -  Presence of a severe infection: pneumonitis and / or chronic diarrhea, or infection
             with herpes viruses or parainfluenza type 3 or adenovirus, or disseminated BCG
             infection, or presence of severe diarrhea and a severe compromise of the general state
             with denutrition

          -  Or failure of a HLA HAPLO-identical bone marrow transplant within 10 years after

          -  In all cases:

               -  No family background of cancer in childhood.

               -  No cytogenetic abnormalities (medullary karyotype) and no detection of main
                  rearrangements associated with acute leukemia of children

               -  Parental/guardian voluntary consent

        Exclusion criteria :

          -  Atypical health with autologous T> 500/ml3

          -  Infection by HIV 1 or 2

          -  Allogeneic HSC completed (excluding situations of failure)

          -  Existence of an HLA identical family donor or HLA identical unrelated donor

          -  No severe infections in a child with a preserved general state

          -  Family background of cancer in childhood

          -  Detection of cytogenetic abnormality and / or rearrangement associated with acute
             leukemia of children

          -  No affiliation to a social security scheme (beneficiary or assignee)




N/A - 12 Months

Accepts Healthy Volunteers



Alain Fischer, MD, PhD, , 

Location Countries


Location Countries


Administrative Informations



Organization ID


Secondary IDs


Responsible Party


Study Sponsor

Assistance Publique - Hôpitaux de Paris

Study Sponsor

Alain Fischer, MD, PhD, Study Director, Assistance Publique - Hôpitaux de Paris

Verification Date

November 2015