This trial is active, not recruiting.

Condition wiskott-aldrich syndrome
Treatment autologous cd34 positive cells transduced with was encoding lentiviral vector.
Phase phase 1/phase 2
Sponsor IRCCS San Raffaele
Collaborator Fondazione Telethon
Start date April 2010
End date April 2018
Trial size 8 participants
Trial identifier NCT01515462, Eudract 2009-017346-32


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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment

Primary Outcomes

Conditioning regimen-related safety
time frame: two months after gene therapy
Safety of lentivirus gene transfer into HSC
time frame: 3 years
Sustained engraftment of genetically corrected haematopoietic stem cells in peripheral blood and/or in bone marrow
time frame: 1 year
Expression of vector-derived WASP
time frame: 1 year
Improved T-cell functions
time frame: 3 years
Antigen-specific responses to vaccination
time frame: 1year
Improved platelet count and MPV normalization
time frame: 3 years
overall survival
time frame: 3 years

Secondary Outcomes

Lack of immune response to transgene
time frame: 3 years
Reduced frequency of severe infections
time frame: 3 years
Reduced bruising and bleeding episodes
time frame: 3 years
Reduced autoimmunity phenomena and eczema
time frame: 3 years
Improved quality of life
time frame: 3 year
Multilineage engraftment of genetically corrected cells
time frame: 3 years
Overall safety of the treatment
time frame: 8 years

Eligibility Criteria

Male participants of any age.

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.

Additional Information

Official title A Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome
Principal investigator Alessandro Aiuti, MD, PhD
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. We expect to treat 8 patients with genetically modified autologous hematopoietic stem cells that were collected from bone marrow and/or mobilized from peripheral blood, and transduced with a lentiviral vector encoding for WAS. The patients are selected according to disease severity (genetic mutation, WASP expression and clinical score), absence of a human leukocyte antigen (HLA)-identical sibling or adequate unrelated donor, age and clinical features. A conditioning regimen based on low doses of iv busulfan (non-myeloablative), Fludarabine and anti-CD20 antibody will be administered to the patients to make space in the bone marrow for gene corrected stem cells, deplete the lymphoid compartment of potentially autoreactive lymphocytes and prevent lymphoproliferative disorder. Patients with autoimmune manifestations could also receive ATG Thymoglobuline to target auto-reactive memory T lymphocytes. This reduced intensity conditioning schedule will provide less toxicity than current preparatory regimens, used in standard allogeneic hematopoietic stem cells transplantation. The treated patients will be followed for 3 years and thereafter monitored for efficacy and safety for additional 5 years.
Trial information was received from ClinicalTrials.gov and was last updated in March 2015.
Information provided to ClinicalTrials.gov by IRCCS San Raffaele.