Wiskott-Aldrich Syndrome
Conditions
Keywords
Wiskott-Aldrich Syndrome, Primary immune deficiency, ex vivo gene therapy, hematopoietic stem cells
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.
Interventions
transplantation of patient's autologous CD34+ cells transduced with lentiviral vector containing human WAS gene
Sponsors
Hôpital Necker-Enfants Malades
Genethon
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in the eczema status | 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 | 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 | 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 frequency and severity of autoimmune disorders | 2 years | 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 | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evidence of sustained engraftment of WASP-expressing transduced cells | 6 weeks, 1, 3, 6, 9, 12, 18 & 24 months | Quantification of vector copy numbers and detection of vector-derived WASP expression |
| Occurrence and type of adverse events | 2 years | Occurrence and type of adverse events reported during the course of the study |
| Reconstitution of humoral and cell mediated immunity | 9, 12, 18 & 24 months | Reconstitution of humoral and cell mediated immunity as compared with the baseline evaluation at study entry |
| Change in medical conditions | 2 years | Assessment of weight, vital signs, ECG and laboratory exams during the course of the study |
| Safety of lentivirus gene transfer into Hematopoietic Stem Cells | 3, 6, 12, 24 months / 6, 12, 18, 24 months | Detection of replication competent lentivirus (RCL) and lentivirus integration sites analysis |
| Improvement of microthrombocytopenia | 3, 6, 12, 24 months | Improvement of microthrombocytopenia as compared with the baseline evaluation at study entry |
| Decrease in the number and volume of platelets transfusions | 2 years | 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 |
Countries
France
Outcome results
None listed