• Wiskott Aldrich Syndrome (WAS) Gene Therapy Clinical Trial

    Gene Therapy

    Phone: 617-632-5064  

    Note: This study has reached the target number of patients to be treated, and accrual for the trial is currently closed.

    Wiskott-Aldrich syndrome (WAS) is a rare genetic immunodeficiency that keeps a child's immune system from functioning properly. It also makes it difficult for a child's bone marrow to produce platelets, making a child prone to bleeding. The traditional standard therapy for Wiskott-Aldrich syndrome is allogeneic stem cell transplant, but this often has suboptimal outcomes.

    In our Wiskott-Aldrich syndrome gene therapy trial, autologous CD34+ bone marrow or peripheral blood stem cells are collected from the patient and transduced ex vivo with a lentiviral gene transfer vector, then infused back into the patient after high dose chemotherapy with busulfan and fludarabine. Such an approach is suitable for patients who lack well-matched donors and avoids allogeneic complications such as graft-versus-host disease (GVHD) and rejection.

    This trial will test wheth­er this approach is safe and whether gene transfer will lead to immunologic and hematologic reconstitution. The costs of research aspects of the protocol are provided for patients treated on the trial by the Gene Therapy Resource Program, NHLBI and NIH.

    Inclusion criteria

    • Confirmed molecular diagnosis by DNA sequencing
    • Severe disease indicated by EITHER -Absence of WAS pro­tein by flow cytometry AND mutation predictive of severe disease (i.e. nonsense, frameshift or large deletion muta­tion) OR-Clinical score 3-5
    • Age 3 months to 35 years
    • Adequate organ function and performance status

    For subjects < 5 years of age:

    • Lack of HLA-genotypically identical sibling bone marrow donor.
    • Lack of a 9/10 or 10/10 molecularly HLA-matched unrelated donor after 3 months of searching.
    • Lack of a 6/6 molecularly HLA-matched cord blood donor of adequate cell number after 3 months of searching.

    For subjects 5 years of age or older:

    • Lack of HLA-genotypically identical sibling bone marrow donor

    Subjects who have previously undergone allogeneic trans­plant and demonstrate:

    • Failure defined as <5% donor T cell engraftment and
    • Contraindication to re-use of the same donor due to severe GVHD or non-availability.

    Exclusion criteria

    • Contraindication to stem cell collection, or to administra­tion of conditioning medication.
    • Known positive HIV serology or HIV nucleic acid testing.
    • Active malignancy other than EBV lymphoproliferative disease.
    • Known myelodysplasia of the bone marrow or abnormal bone marrow cytogenetics.
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