Phase I/II Clinical Trial of Haematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Genethon
- Enrollment
- 5
- Locations
- 2
- Primary Endpoint
- Improvement in the eczema status
Study Overview
Brief Summary
This is a phase I/II study to evaluate the safety and efficacy of Hematopoietic Stem Cell genetherapy for the Wiskott-Aldrich Syndrome.
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Sex
- 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
Outcomes
Primary Outcomes
Improvement in the eczema status
Time Frame: 2 years
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
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
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 number of disease related days of hospitalization
Time Frame: 2 years
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
Reduction in the frequency and severity of autoimmune disorders
Time Frame: 2 years
Reduction in the frequency and severity of autoimmune disorders as compared with the baseline status at study entry
Secondary Outcomes
- Improvement of microthrombocytopenia(3, 6, 12, 24 months)
- Evidence of sustained engraftment of WASP-expressing transduced cells(6 weeks, 1, 3, 6, 9, 12, 18 & 24 months)
- Change in medical conditions(2 years)
- Reconstitution of humoral and cell mediated immunity(9, 12, 18 & 24 months)
- Safety of lentivirus gene transfer into Hematopoietic Stem Cells(3, 6, 12, 24 months / 6, 12, 18, 24 months)
- Decrease in the number and volume of platelets transfusions(2 years)
- Occurrence and type of adverse events(2 years)