Clinical trial NCT01515462: Gene Therapy for Wiskott-Aldrich Syndrome
Official title: A Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Wiskott-Aldrich Syndrome (WAS)
Keywords: Lentiviral vector
Gene therapy
Wiskott-Aldrich Syndrome
TLT003
Previously GSK2696275
Previously OTL-103
Lead sponsor: Fondazione Telethon
Sponsor class: OTHER
Collaborators: name: Ospedale San Raffaele
First posted: 2012-01-24
Enrollment: 8
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This will be a single-arm study. All subjects will receive OTL-103 gene therapy and will be followed up for 15 years post gene therapy
Primary purpose: TREATMENT

Brief summary: This is phase I/II protocol to evaluate the safety and efficacy of WAS gene transfer into hematopoietic stem/progenitor cells for the treatment of Wiskott Aldrich Syndrome.

Detailed description: Wiskott-Aldrich Syndrome (WAS) is an X-linked primary immunodeficiency caused by mutations in the WAS gene which encodes the WAS protein (WASP), a cytoskeletal regulator which is expressed exclusively in hematopoietic cells.

Eligibility criteria: Inclusion Criteria:

1. Diagnosis of WAS defined by genetic mutation and at least one of the following criteria:

   * Severe WAS mutation
   * Absence of WASP expression
   * Severe clinical score (Zhu clinical score ≥ 3
2. No HLA-identical sibling donor
3. Negative search for a matched unrelated donor (10/10) or an adequate unrelated cord blood donor (5-6/6) within 4-6 months

   * Patients of \> 5 years of age who are not candidate to unrelated allogeneic transplant based on clinical conditions.
4. Parental/guardian/patient signed informed consent.

Exclusion Criteria:

1. Patients positive for HIV-infection.
2. Patients affected by neoplasia.
3. Patients with cytogenetic alterations typical of MDS/AML.
4. Patients with end-organ functions or any other severe disease which, in the judgement of the investigator, would make the patient inappropriate for entry into this study.
5. Patients who underwent an allogeneic haematopoietic stem cell transplantation in the previous 6 months.
6. Patients who underwent an allogeneic haematopoietic stem cell transplantation with evidence of residual cells of donor origin.

Primary outcomes:
measure: Safety of Reduced Conditioning Regimen
timeFrame: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)
measure: Safety of Lentivirus Gene Transfer Into HSC
timeFrame: after 48 hours after Telethon003 infusion
measure: Sustained Engraftment of Genetically Corrected Haematopoietic Stem Cells in Peripheral Blood and/or in Bone Marrow
timeFrame: at 1 year after Telethon003 infusion
measure: Presence of Detectable Vector-derived WASP
timeFrame: Median duration: 11.1 years (range: 8.01 -13.3 years)
measure: Improved T-cell Functions
timeFrame: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)
measure: Antigen-specific Responses to Vaccination
timeFrame: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)
measure: Improved Platelet Count and MPV Normalization
timeFrame: up to 3 years after Telethon003 infusion
measure: Overall Survival
timeFrame: Follow up phase - Median duration: 11.1 years (range: 8.01 -13.3 years)
Secondary outcomes:
measure: Lack of Immune Response to Transgene
timeFrame: up to 3 years after Telethon003 infusion
measure: Reduced Frequency of Severe Infections
timeFrame: up to 3 years after Telethon003 infusion
measure: Reduced Bruising and Bleeding Episodes
timeFrame: 3 years
measure: Reduced Autoimmunity Phenomena and Eczema
timeFrame: 3 years
measure: Improved Quality of Life
timeFrame: 3 year
measure: Multilineage Engraftment of Genetically Corrected Cells
timeFrame: 3 years
measure: Overall Safety of the Treatment
timeFrame: 8 years
Other outcomes:
Locations:
city: Milan
country: Italy
facility: Ospedale San Raffaele - Telethon Institute for Gene Therapy (OSR-TIGET)
Study officials:
References:
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