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Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID2)

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01410019
First received: June 21, 2011
Last updated: June 17, 2014
Last verified: June 2014

June 21, 2011
June 17, 2014
December 2010
July 2015   (final data collection date for primary outcome measure)
Assessment of immunological reconstitution at short term [ Time Frame: month 4 ] [ Designated as safety issue: Yes ]
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
Assessment of immunological reconstitution at short term [ Time Frame: month 4 ] [ Designated as safety issue: Yes ]
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
Complete list of historical versions of study NCT01410019 on ClinicalTrials.gov Archive Site
  • 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 ] [ Designated as safety issue: Yes ]
    PCR of vector
  • Analysis of activated proto-oncogene s expression [ Time Frame: every 4 months during 2 years and every 6 months indefinitely ] [ Designated as safety issue: Yes ]
    Immunofluorescence analysis of the relative expression of different families of TCR alpha beta et gamma delta LAM PCR analysis and sequencing of integration sites
  • 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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    Immunofluorescence analysis of the relative expression of different families of TCR alpha beta et gamma delta LAM PCR analysis and sequencing of integration sites
Not Provided
Not Provided
 
Gene Therapy for X-linked Severe Combined Immunodeficiency
Protocol No. 2 of Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1) Using a Self Retroviral Vector - SCID2

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.

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.
Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
X-linked Severe Combined Immunodeficiency
Other: Gene transfer
Single infusion of autologous CD34+ cells transduced with the self-inactivating (SIN) GAMMARETROVIRAL vector pSRS11.EFS.IL2RG.pre
Other Name: Gene transfer
Experimental: 1
Gene transfer
Intervention: Other: Gene transfer

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
5
January 2016
July 2015   (final data collection date for primary outcome measure)

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)
Male
up to 12 Months
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT01410019
P071204, 2008-002380-14
Yes
Assistance Publique - Hôpitaux de Paris
Assistance Publique - Hôpitaux de Paris
Not Provided
Study Director: Alain Fischer, MD, PhD AP-HP
Assistance Publique - Hôpitaux de Paris
June 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP