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Gene Therapy for WAS

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Genethon
Sponsor:
Collaborator:
Hôpital Necker-Enfants Malades
Information provided by:
Genethon
ClinicalTrials.gov Identifier:
NCT01347346
First received: May 3, 2011
Last updated: November 24, 2014
Last verified: November 2014
  Purpose

This is a phase I/II study to evaluate the safety and efficacy of Hematopoietic Stem Cell genetherapy for the Wiskott-Aldrich Syndrome.


Condition Intervention Phase
Wiskott-Aldrich Syndrome
Genetic: Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene
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: 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:
  • Improvement in the eczema status [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Improvement in eczema status as compared with the baseline status at study entry on clinical evaluation

  • Reduction in the frequency and severity of infection episodes [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Reduction in the frequency and severity of infection episodes as compared with the baseline status and the patient's historical data collected over the 2 years prior to study entry

  • Reduction in the frequency and severity of bruising and bleeding episodes [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Reduction in the frequency and severity of bruising and bleeding episodes as compared with the baseline status and the patient's historical data collected over the 2 years prior to study entry

  • Reduction in the frequency and severity of autoimmune disorders [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Reduction in the frequency and severity of autoimmune disorders as compared with the baseline status at study entry

  • Reduction in the number of disease related days of hospitalization [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Reduction in the number of disease related days of hospitalization as compared with the patient's historical data collected over the 2 years prior to study entry


Secondary Outcome Measures:
  • Occurrence and type of adverse events [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Occurrence and type of adverse events reported during the course of the study

  • Change in medical conditions [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    Assessment of weight, vital signs, ECG and laboratory exams during the course of the study

  • Safety of lentivirus gene transfer into Hematopoietic Stem Cells [ Time Frame: 3, 6, 12, 24 months / 6, 12, 18, 24 months ] [ Designated as safety issue: Yes ]
    Detection of replication competent lentivirus (RCL) and lentivirus integration sites analysis

  • Improvement of microthrombocytopenia [ Time Frame: 3, 6, 12, 24 months ] [ Designated as safety issue: No ]
    Improvement of microthrombocytopenia as compared with the baseline evaluation at study entry

  • Decrease in the number and volume of platelets transfusions [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Decrease in the number and volume of platelets transfusions as compared with patient's historical data collected over the 2 years prior to study entry

  • Evidence of sustained engraftment of WASP-expressing transduced cells [ Time Frame: 6 weeks, 1, 3, 6, 9, 12, 18 & 24 months ] [ Designated as safety issue: No ]
    Quantification of vector copy numbers and detection of vector-derived WASP expression

  • Reconstitution of humoral and cell mediated immunity [ Time Frame: 9, 12, 18 & 24 months ] [ Designated as safety issue: No ]
    Reconstitution of humoral and cell mediated immunity as compared with the baseline evaluation at study entry


Estimated Enrollment: 5
Study Start Date: May 2011
Estimated Primary Completion Date: December 2017 (Final data collection date for primary outcome measure)
Intervention Details:
    Genetic: Autologous CD34 positive cells transduced with a lentiviral vector containing human WAS gene
    transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing human WAS 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.

  Eligibility

Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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 ClinicalTrials.gov identifier: NCT01347346

Locations
France
Hôpital Necker-Enfants Malades Recruiting
Paris, France, 75015
Contact: Fischer Alain, MD, PHD       fischer@necker.fr   
Contact: Cavazzana-Calvo Marina, MD, PHD       m.cavazzana@nck.aphp.fr   
Principal Investigator: Adrian Thrasher, MD, PHD         
Sponsors and Collaborators
Genethon
Hôpital Necker-Enfants Malades
  More Information

No publications provided

Responsible Party: Alain Fischer, Hôpital Necker-Enfants Malades
ClinicalTrials.gov Identifier: NCT01347346     History of Changes
Other Study ID Numbers: GTG003.08, 2009-011152-22
Study First Received: May 3, 2011
Last Updated: November 24, 2014
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:
Syndrome
Wiskott-Aldrich Syndrome
Immunologic Deficiency Syndromes
Blood Coagulation Disorders
Blood Coagulation Disorders, Inherited
Disease
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Hematologic Diseases
Hemorrhagic Disorders
Immune System Diseases
Leukocyte Disorders
Leukopenia
Lymphopenia
Pathologic Processes

ClinicalTrials.gov processed this record on November 24, 2014