Gene Therapy for WAS

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2011 by Genethon.
Recruitment status was  Recruiting
Hôpital Necker-Enfants Malades
Information provided by:
Genethon Identifier:
First received: May 3, 2011
Last updated: June 15, 2011
Last verified: June 2011

This clinical trial is an ex vivo gene therapy trial. It consists in the correction of the genetic mutation harbored by patients with Wiskott-Aldrich Syndrome, through patients' own haematopoietic stem cells transplantation after modification with a lentiviral vector expressing the human Wiskott-Aldrich Syndrome protein gene.

Condition Intervention Phase
Wiskott-Aldrich Syndrome
Biological: ex vivo gene therapy
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Clinical Trial of Haematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome

Resource links provided by NLM:

Further study details as provided by Genethon:

Primary Outcome Measures:
  • number of patients safely receiving the conditioning regimen [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
    safety of conditioning regimen is measured by hematopoietic recovery within 6 weeks.

  • number of patients whose stem cells are safely transduced [ Time Frame: 1 week ] [ Designated as safety issue: Yes ]

    safety of transduction procedure is determined prior to transplantation and is assessed through:

    • transduced cells number determination
    • cell viability measure
    • RCL detection

  • number of patients with engraftment of genetically corrected hematopoietic progenitors/differentiated cells [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    engraftment is assessed by evidence of vector sequences or transgene expression in the cells.

  • number of patients with reconstituted cell mediated and humoral immunity [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    reconstitution of cell mediated and humoral immunity is assessed by evidence of changes in T cell function and circulating immunoglobulin levels

  • number of patients with corrected microthrombocytopenia [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    correction of microthrombocytopenia is assessed by blood platelet counts, expected to rise above 50,000/mm3

Secondary Outcome Measures:
  • number of patients with reduced frequency of infection [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    reduction in frequency of infection is evaluated by clinical histroy, complete physical examinations, heamatological and microbiological tests

  • number of patients with resolution/reduction of autoimmunity [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    resolution/reduction of autoimmunity is considered as a decrease from baseline observations assessed by clinical examination

  • number of patients with improvement in eczema [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    improvement of eczema is considered as a decrease from baseline observations assessed by clinical examinations

  • number of patients with reduction in bruising and bleeding episodes [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    reduction in bruising and bleeding episodes is assessed by clinical monitoring

Estimated Enrollment: 5
Study Start Date: May 2011
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: ex vivo gene therapy
    transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing human WASP gene
Detailed Description:

This clinical trial is an ex vivo gene therapy trial. the investigational product corresponds to autologous CD34+ cells transduced with a lentiviral vector harboring the human WASP gene.


Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • males of all ages
  • severe WAS (clinical score 3-5) or absence of WAS protein in peripheral blood mononuclear cells determined by Western blotting and flow cytometry
  • molecular confirmation by WAS gene DNA sequencing
  • lack of HLA-genotypically identical bone marrow after 3 month search
  • lack of a 10/10 or 9/10 antigen HLA-matched unrelated donor after 3 month search
  • lack of a HLA-matched cord blood after 3 month search
  • parental, guardian, patient signed informed consent/assent
  • willing to return for follow-up
  • only for patients who have received previous allogenic hematopoietic stem cell transplant:
  • failed allogenic hematopoietic stem cell transplant
  • contraindication to repeat transplantation

Exclusion Criteria:

  • patient with HLA-genotypically identical bone marrow
  • patient with 10/10 or 9/10 antigen HLA-matched unrelated donor or with HLA-matched cord blood
  • contraindication to leukapheresis
  • contraindication to bone marrow harvest
  • contraindication to administration of conditioning medication
  • HIV positive patient
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01347346

Hôpital Necker-Enfants Malades Recruiting
Paris, France, 75015
Contact: Fischer Alain, MD, PHD   
Contact: Cavazzana-Calvo Marina, MD, PHD   
Principal Investigator: Adrian Thrasher, MD, PHD         
Sponsors and Collaborators
Hôpital Necker-Enfants Malades
  More Information

No publications provided

Responsible Party: Alain Fischer, Hôpital Necker-Enfants Malades Identifier: NCT01347346     History of Changes
Other Study ID Numbers: GTG003.08, 2009-011152-22
Study First Received: May 3, 2011
Last Updated: June 15, 2011
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Genethon:
Wiskott-Aldrich Syndrome
Primary immune deficiency
ex vivo gene therapy
hematopoietic stem cells

Additional relevant MeSH terms:
Wiskott-Aldrich Syndrome
Pathologic Processes
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhagic Disorders
Leukocyte Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Immunologic Deficiency Syndromes
Immune System Diseases processed this record on October 19, 2014