Gene Therapy for X-linked Severe Combined Immunodeficiency


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.

Full Title of Study: “Protocol No. 2 of Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1) Using a Self Retroviral Vector – SCID2”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: N/A
    • Intervention Model: Single Group Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: July 2015

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.


  • Other: Gene transfer
    • Single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) GAMMARETROVIRAL vector pSRS11.EFS.IL2RG.pre

Arms, Groups and Cohorts

  • Experimental: 1
    • Gene transfer

Clinical Trial Outcome Measures

Primary Measures

  • Assessment of immunological reconstitution at short term
    • Time Frame: month 4
    • T cells proliferation T cells and B cells repertory by immunofluorescence T, NK and B Lymphocytes phenotyping Immunoglobulins dosage IgG, A, M, E and antibody production

Secondary Measures

  • Molecular characterization of gene transfer
    • Time Frame: every 15 days during 3 months, once per month until 6 months, every 3 months until year 1, every year until year 10
    • PCR of vector
  • Analysis of activated proto-oncogene s expression
    • Time Frame: every 4 months during 2 years and every 6 months indefinitely
    • Immunofluorescence analysis of the relative expression of different families of TCR alpha beta et gamma delta LAM PCR analysis and sequencing of integration sites

Participating in This Clinical Trial

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 transplantation – 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)

Gender Eligibility: Male

Minimum Age: N/A

Maximum Age: 12 Months

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Assistance Publique – Hôpitaux de Paris
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Alain Fischer, MD, PhD, Study Director, Assistance Publique – Hôpitaux de Paris


Cavazzana-Calvo M, Hacein-Bey S, de Saint Basile G, Gross F, Yvon E, Nusbaum P, Selz F, Hue C, Certain S, Casanova JL, Bousso P, Deist FL, Fischer A. Gene therapy of human severe combined immunodeficiency (SCID)-X1 disease. Science. 2000 Apr 28;288(5466):669-72.

Hacein-Bey-Abina S, Le Deist F, Carlier F, Bouneaud C, Hue C, De Villartay JP, Thrasher AJ, Wulffraat N, Sorensen R, Dupuis-Girod S, Fischer A, Davies EG, Kuis W, Leiva L, Cavazzana-Calvo M. Sustained correction of X-linked severe combined immunodeficiency by ex vivo gene therapy. N Engl J Med. 2002 Apr 18;346(16):1185-93.

Hacein-Bey-Abina S, Hauer J, Lim A, Picard C, Wang GP, Berry CC, Martinache C, Rieux-Laucat F, Latour S, Belohradsky BH, Leiva L, Sorensen R, Debré M, Casanova JL, Blanche S, Durandy A, Bushman FD, Fischer A, Cavazzana-Calvo M. Efficacy of gene therapy for X-linked severe combined immunodeficiency. N Engl J Med. 2010 Jul 22;363(4):355-64. doi: 10.1056/NEJMoa1000164.

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