Clinical trial NCT01347346: Gene Therapy for WAS
Official title: Phase I/II Clinical Trial of Haematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Wiskott-Aldrich Syndrome
Keywords: Wiskott-Aldrich Syndrome
Primary immune deficiency
ex vivo gene therapy
hematopoietic stem cells
Lead sponsor: Genethon
Sponsor class: OTHER
Collaborators: name: Hôpital Necker-Enfants Malades
First posted: 2011-05-04
Enrollment: 5
Sex: MALE
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Improvement in the eczema status
timeFrame: 2 years
measure: Reduction in the frequency and severity of infection episodes
timeFrame: 2 years
measure: Reduction in the frequency and severity of bruising and bleeding episodes
timeFrame: 2 years
measure: Reduction in the frequency and severity of autoimmune disorders
timeFrame: 2 years
measure: Reduction in the number of disease related days of hospitalization
timeFrame: 2 years
Secondary outcomes:
measure: Occurrence and type of adverse events
timeFrame: 2 years
measure: Change in medical conditions
timeFrame: 2 years
measure: Safety of lentivirus gene transfer into Hematopoietic Stem Cells
timeFrame: 3, 6, 12, 24 months / 6, 12, 18, 24 months
measure: Improvement of microthrombocytopenia
timeFrame: 3, 6, 12, 24 months
measure: Decrease in the number and volume of platelets transfusions
timeFrame: 2 years
measure: Evidence of sustained engraftment of WASP-expressing transduced cells
timeFrame: 6 weeks, 1, 3, 6, 9, 12, 18 & 24 months
measure: Reconstitution of humoral and cell mediated immunity
timeFrame: 9, 12, 18 & 24 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
Study officials:
References:
citation: Magnani A, Semeraro M, Adam F, Booth C, Dupre L, Morris EC, Gabrion A, Roudaut C, Borgel D, Toubert A, Clave E, Abdo C, Gorochov G, Petermann R, Guiot M, Miyara M, Moshous D, Magrin E, Denis A, Suarez F, Lagresle C, Roche AM, Everett J, Trinquand A, Guisset M, Bayford JX, Hacein-Bey-Abina S, Kauskot A, Elfeky R, Rivat C, Abbas S, Gaspar HB, Macintyre E, Picard C, Bushman FD, Galy A, Fischer A, Six E, Thrasher AJ, Cavazzana M. Long-term safety and efficacy of lentiviral hematopoietic stem/progenitor cell gene therapy for Wiskott-Aldrich syndrome. Nat Med. 2022 Jan;28(1):71-80. doi: 10.1038/s41591-021-01641-x. Epub 2022 Jan 24.