Haploidentical Hematopoietic Stem Cell Transplantation Patients With Wiskott-Aldrich Syndrome

Haploidentical Hematopoietic Stem Cell Transplantation for Pediatric Patients With Wiskott-Aldrich Syndrome: A Pilot Study

Wiskott - Aldrich syndrome (WAS) is a rare disorder curable only through allogeneic hematopoietic stem cell transplantation. A mismatched family member is an option when no human leukocyte antigen (HLA-immune system type) matched related or matched unrelated donor is available.

This study will evaluate a novel therapeutic strategy for patients with WAS who undergo haploidentical transplantation using a parental donor. To reduce the risk of transplant-related toxicities, participants will receive a reduced intensity chemotherapy and antibody regimen (conditioning treatment). Participants will then receive an infusion of donor stem cells depleted of certain white blood cells called T- and B-lymphocytes. The stem cell depletion processing will be done through the use of the investigational CliniMACS device. A certain number of T-lymphocytes will be added back to the processed stem cell graft prior to infusion into the recipient.

The primary objective of this study is to determine the safety of haploidentical transplantation in WAS patients using this specified conditioning regimen and engineered graft. Safety will be defined in terms of engraftment (meaning how well the graft grows and functions after infusion) and regimen-related toxicity within the first 100 days after transplant.

Secondary Objectives in this trial include the following:

• To estimate the survival of study recipients at one year after infusion of the T- and B-lymphocyte depleted stem cell graft.
• To assess if the study treatment enables the recipient to generate normal donor-derived B-cell numbers and endogenous IgM, IgG, and IgA production, resulting in a reduction/elimination of the need for intravenous immunoglobulin infusions.
• To determine if the study treatment results in the ability of the research participant to generate normal donor-derived T cell response and natural killer (NK) cell numbers and function.
• To describe the incidence of Epstein-Barr virus-lymphoproliferative disease (EBV-LPD) in these transplant recipients.

Inclusion Criteria:

• Genotypical diagnosis of Wiskott-Aldrich Syndrome.
• Less than 18 years of age at time of transplant.

Must meet two of the eight following clinical criteria:

• Eczema that is refractory to standard therapy.
• Thrombocytopenia as defined by a platelet count < 50,000/mm3.
• Significant risk for or presence of opportunistic infection.
• Autoimmune disease.
• Malignancy or pre-malignant condition.
• Family history as defined as a family member with WAS who died before 10 years of age.
• Does not have a suitable, available 6/6 HLA-matched sibling donor available for donation.
• Does not have a suitable, available 10/10 HLA-allele matched unrelated donor identified through the National Marrow Donor Program (NMDP).

Exclusion Criteria:

If any of the following clinical indicators are met within 45 days prior to transplant, the research participant will not be eligible for the study:

• Symptomatic cardiac disease or evidence of significant cardiac dysfunction by echocardiogram (shortening fraction < 30%).
• Creatinine clearance or Tc 99 less than or equal 40ml/min/1.73 m2.
• SGPT greater than or equal 500 U/L.
• Karnofsky or Lansky Performance Score of < 50.
• Pulmonary function tests: FVC < 50% of predicted value if age appropriate to perform the testing adequately or an O2 saturation less than or equal to 92% on room air at rest.