Pilot and Feasibility Study of Hematopoietic Stem Cell Gene Transfer for the Wiskott-Aldrich Syndrome

Plain-language summary

Wiskott-Aldrich Syndrome (WAS) is an inherited blood and bone marrow disorder carried on the X chromosome that affects boys: their platelets are low in number and do not work properly, and their white blood cells function poorly, leading to risks of severe bleeding, infection, eczema, arthritis and lymphoma. This Phase 1/2 study evaluates retrovirus-mediated gene transfer. It enrolls participants aged 3 months to 35 years with a molecular diagnosis confirmed by DNA sequencing and no suitably HLA-matched donor available.

The summary above is a plain-language rendering of the official record. The original English title is shown for reference.

Trial details

Phase

PHASE1/PHASE2

Status

Completed

Sponsor

David Williams

Intervention

Retrovirus-mediated gene transfer

Start date

7/1/2011

Estimated completion

9/1/2024

Countries

United States

Related genes

Locations

• Boston, United States

Eligibility criteria

Criteria are reproduced from the ClinicalTrials.gov record in the original English. Only the trial team can determine eligibility.

Inclusion Criteria:

1. Confirmed molecular diagnosis by DNA sequencing and either

   1. absence of the WAS protein by flow cytometry OR
   2. clinical score 3-5
2. Age 3 months to 35 years
3. For subjects \< 5 years of age:

   1. Lack of HLA-genotypically identical bone marrow donor.
   2. Lack of a 9/10 or 10/10 molecularly HLA-matched unrelated donor after 3 months of searching.
   3. Lack of a 6/6 molecularly HLA-matched cord blood donor of adequate cell number after 3 months of searching
4. For subjects 5 years of age or older:

   a.Lack of HLA-genotypically identical bone marrow donor.
5. Subjects who have undergone allogeneic transplant previously must additionally have:

   1. Failure defined as \<5% donor T cell engraftment and
   2. Contraindication to re-use of the same donor due to severe GVHD or non-availability.
6. Parental/guardian/patient signed informed consent
7. Willingness to return for follow-up during the 5 year study period.
8. Adequate organ function and performance status

   1. Performance status ≥50% (Lansky play for age \<16 years, Karnofsky for age ≥16 years)
   2. Left ventricular ejection fraction \>40% or shortening fraction \>25%
   3. Bilirubin ≤ 2.0 mg/dL
   4. Measured creatinine clearance or GFR by nuclear medicine study ≥40 ml/min/1.73 m2
   5. DLCO (corrected for hemoglobin), FEV1, FVC \>50% of predicted; if age \< 7 years, then oxygen saturation \>92% on room air

Exclusion Criteria:

1. Contraindication to bone marrow harvest, or to administration of conditioning medication.
2. Known positive HIV serology or HIV nucleic acid testing.
3. Other uncontrolled infection.
4. Active malignancy other than EBV lymphoproliferative disease.
5. Known myelodysplasia of the bone marrow or abnormal bone marrow cytogenetics
6. Congenital cardiac disease with congestive heart failure
7. Oxygen dependence at baseline
8. Any other condition that, in the opinion of the Investigator, may compromise the safety or compliance of the patient or would preclude the patient from successful study completion. This may include but is not limited to:

   * Severe deterioration of clinical condition after collection of cells but before infusion of transduced cells
   * Documented refusal or inability of the family to return for scheduled visits
   * Other concerns about unwillingness or inability to comply with protocol requirements
   * Unforeseen rare circumstances such as sudden loss of legal guardianship