Clinical Trial: Gene Therapy for X-linked Severe Combined Immunodeficiency

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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 Summary:

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.

Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: 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


Original Primary Outcome: 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 Immunofluorescence gamma c Immunoglobulins dosage IgG, A, M, E and antibody production


Current Secondary Outcome:

  • 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


Original Secondary Outcome:

  • 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 4 ]
    PCR and RT-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


Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: June 21, 2011
Date Started: December 2010
Date Completion: October 2016
Last Updated: August 25, 2016
Last Verified: November 2015