Try our beta test site
IMPORTANT: Listing of a study on this site does not reflect endorsement by the National Institutes of Health. Talk with a trusted healthcare professional before volunteering for a study. Read more...

Gene Therapy for Wiskott-Aldrich Syndrome (TIGET-WAS)

This study is ongoing, but not recruiting participants.
Fondazione Telethon
Information provided by (Responsible Party):
Alessandro Aiuti, IRCCS San Raffaele Identifier:
First received: December 23, 2011
Last updated: March 5, 2015
Last verified: March 2015
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.

Condition Intervention Phase
Wiskott-Aldrich Syndrome
Genetic: Autologous CD34 positive cells transduced with WAS encoding lentiviral vector.
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Clinical Trial of Hematopoietic Stem Cell Gene Therapy for the Wiskott-Aldrich Syndrome

Resource links provided by NLM:

Further study details as provided by IRCCS San Raffaele:

Primary Outcome Measures:
  • Conditioning regimen-related safety [ Time Frame: two months after gene therapy ]
    Absence of engraftment failure or prolonged aplasia (<500/ul ANC with no evidence of bone marrow recovery) and surveillance of non haematological regimen related toxicity (for clinical features NCI >2, for metabolic/laboratory NCI >3)

  • Safety of lentivirus gene transfer into HSC [ Time Frame: 3 years ]

    short-term safety and tolerability of lentiviral-transduced cell infusion

    -long-term safety of lentiviral-transduced cell infusion (absence of Replication Competent Lentivirus (RCL) and abnormal clonal proliferation).

  • Sustained engraftment of genetically corrected haematopoietic stem cells in peripheral blood and/or in bone marrow [ Time Frame: 1 year ]
    ≥ 0.04 Vector copy number (VCN)/cell in bone marrow CD34+ or ≥0.1 VCN/cell in peripheral blood T lymphocytes

  • Expression of vector-derived WASP [ Time Frame: 1 year ]
    Detection of vector-derived WASP expression by FACS analyses and/or Western Blot

  • Improved T-cell functions [ Time Frame: 3 years ]
    Improvement in in vitro T cell proliferation and/or IL-2 secretion upon stimulation with anti-CD3i as compared to pre-gene therapy values.

  • Antigen-specific responses to vaccination [ Time Frame: 1year ]
    Ability to mount a humoral response to nominal antigens including antibodies to T cell dependent antigens (Tetanus Toxoid) and unconjugated polysaccharide antigens (Peumococcus, Meningococcus), measured after vaccination (foreseen >1 year after gene therapy). Positive cellular response to Tetanus Toxoid after vaccination measured by in vitro proliferative response >1 year after gene therapy.

  • Improved platelet count and MPV normalization [ Time Frame: 3 years ]
    Sustained increase in platelet count compared to baseline, analysing the individual longitudinal profile

  • overall survival [ Time Frame: 3 years ]
    number of patients alive all over the trial

Secondary Outcome Measures:
  • Lack of immune response to transgene [ Time Frame: 3 years ]
    Immunoblot analysis

  • Reduced frequency of severe infections [ Time Frame: 3 years ]
    Decrease in number of severe infections as evaluated in the second and third year after the treatment by clinical history, complete physical examinations, hematological and microbiological tests.

  • Reduced bruising and bleeding episodes [ Time Frame: 3 years ]
    Reduction in bruising and/or bleeding manifestations when present, as assessed by clinical monitoring, compared to clinical history

  • Reduced autoimmunity phenomena and eczema [ Time Frame: 3 years ]
    Reduction in laboratory markers (number and titer of antibody when available) and/or clinical manifestations of autoimmunity, as evaluated by organ-specific and systemic autoantibodies, imaging and clinical follow-up, compared to clinical history. Reduction in eczema as evaluated by clinical score

  • Improved quality of life [ Time Frame: 3 year ]
    Improved quality of life, measured after the first year of treatment by reduced hospitalization, reduced requirement of drugs, school attendance, social activities.

  • Multilineage engraftment of genetically corrected cells [ Time Frame: 3 years ]
    ≥0.04 VCN/cell on all the available peripheral blood and/or bone marrow cell subpopulations (BM subpopulations: GlyA+, CD15+, CD61+, CD3+, CD19+, CD56+; PB subpopulations: CD15+, CD19+, CD56+)

  • Overall safety of the treatment [ Time Frame: 8 years ]
    Recording of AE, AR, SAE/SAR, UAR, SUSAR

Estimated Enrollment: 8
Study Start Date: April 2010
Estimated Study Completion Date: April 2023
Estimated Primary Completion Date: April 2018 (Final data collection date for primary outcome measure)
Intervention Details:
    Genetic: Autologous CD34 positive cells transduced with WAS encoding lentiviral vector.
    The Medicinal Product consists of autologous CD34+ cells collected from the bone marrow and/or peripheral blood and transduced with a lentiviral vector encoding WASP controlled by WAS promoter sequences (w1.6W). Dosage indications: a minimum dose of 2x10^6 CD34+ cells/Kg (maximum 20x10^6 CD34+ cells/Kg) and an optimal dose of 5-10x10^6 CD34+ cells/Kg will be infused i.v.
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.

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.


Ages Eligible for Study:   Child, Adult, Senior
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT01515462

Pediatric clinical research unit, San Raffale Telethon Institute of Gene Therapy
Milano, Italy, 20132
Sponsors and Collaborators
IRCCS San Raffaele
Fondazione Telethon
Principal Investigator: Alessandro Aiuti, MD, PhD San Raffaele Telethon Institute of Gene Therapy, Milan, Italy
  More Information


Responsible Party: Alessandro Aiuti, Head Pediatric Clinical Research Unit, IRCCS San Raffaele Identifier: NCT01515462     History of Changes
Other Study ID Numbers: Eudract 2009-017346-32
Study First Received: December 23, 2011
Last Updated: March 5, 2015

Keywords provided by IRCCS San Raffaele:
Wiskott-Aldrich Syndrome
Lentiviral vector
Gene therapy

Additional relevant MeSH terms:
Wiskott-Aldrich Syndrome
Pathologic Processes
Blood Coagulation Disorders, Inherited
Blood Coagulation Disorders
Hematologic Diseases
Hemorrhagic Disorders
Leukocyte Disorders
Genetic Diseases, Inborn
Genetic Diseases, X-Linked
Immunologic Deficiency Syndromes
Immune System Diseases processed this record on April 24, 2017