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

This study is currently recruiting participants.
Verified May 2013 by Assistance Publique - Hôpitaux de Paris
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01410019
First received: June 21, 2011
Last updated: May 13, 2013
Last verified: May 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
X-linked Severe Combined Immunodeficiency
 Other: Gene transfer
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Protocol No. 2 of Gene Therapy for X-linked Severe Combined Immunodeficiency (SCID-X1) Using a Self Retroviral Vector - SCID2

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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


Secondary Outcome 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 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


Estimated Enrollment: 5
Study Start Date: December 2010
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Gene transfer
 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

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.
  Eligibility

Ages Eligible for Study:   up to 12 Months
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
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 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 or HTLV-1
  • 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)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01410019

Contacts
Contact: Salima Hacein-Bey, MD, PhD 00331444381527 salima.hacein-bey@nck.aphp.fr
Contact: Raphael Serreau, MD, PhD 0033158411180 raphael.serreau@cch.aphp.fr

Locations
France
Hopital Necker Recruiting
Paris, France, 75015
Contact: Marina Cavazzana-Calvo, MD, PhD     0033144495810     m.cavazzana@nck.aphp.fr    
Contact: Salima Hacein-Bey, MD, PhD     0033144381527     salima.hacein-bey@nck.aphp.fr    
Principal Investigator: Alain Fischer, MD, PhD            
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Study Director: Alain Fischer, MD, PhD AP-HP
  More Information

Publications:

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01410019     History of Changes
Other Study ID Numbers: P071204, 2008-002380-14
Study First Received: June 21, 2011
Last Updated: May 13, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
X-linked Severe Combined Immunodeficiency (SCID-X1)
severe infection
gene therapy
HLA identical family donor
without HLA identical unrelated donor

Additional relevant MeSH terms:
Immunologic Deficiency Syndromes
Severe Combined Immunodeficiency
X-Linked Combined Immunodeficiency Diseases
Immune System Diseases
Infant, Newborn, Diseases
 DNA Repair-Deficiency Disorders
Metabolic Diseases
Genetic Diseases, X-Linked
Genetic Diseases, Inborn

ClinicalTrials.gov processed this record on June 17, 2013