Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency

Completed · Phase 1

Conditions studied: Severe Combined Immunodeficiency Syndrome

In brief

This study will evaluate a new method for delivering gene transfer therapy to patients with severe combined immunodeficiency disease (SCID) due to a defective adenosine deaminase (ADA) gene. This gene codes for the adenosine deaminase enzyme, which is essential for the proper growth and function of infection-fighting white blood cells called T and B lymphocytes. Patients who lack this enzyme are vulnerable to frequent and severe infections. Some patients with this disease receive enzyme replacement therapy with weekly injections of the drug PEG-ADA (ADAGEN). This drug may increase the number of immune cells and reduce infections, but it is not a cure. Gene transfer therapy, in which a normal ADA gene is inserted into the patient s cells, attempts to correct the underlying cause of disease. This therapy has been tried in a small number of patients with varying degrees of success. In this study, the gene will be inserted into the patient s stem cells (cells produced by the bone marrow that mature into the different blood components white cells, red cells and platelets). Patients with ADA deficiency and SCID who are taking PEG-ADA and are not candidates for HLA-identical sibling donor bone marrow transplantation may be eligible for this study. Participants will be admitted to the NIH Clinical Center for 2 to 3 days. Stem cells will be collected either from cord blood (in newborn patients) or from the bone marrow. The bone marrow procedure is done under light sedation or general anesthesia. It involves drawing a small amount of marrow through a needle inserted into the hip bone. The stem cells in the marrow will be grown in the laboratory and a normal human ADA gene will be transferred into them through a special type of disabled mouse virus. A few days later, the patient will receive the ADA-corrected cells through an infusion in the vein that will last from 10 minutes to 2 hours. Patients will be evaluated periodically for immune function with blood tests, skin tests, and reactions to tetanus, diphtheria, H. influenza B and S. pneumoniae vaccinations. The survival of ADA-corrected cells will be monitored through blood tests. The number and amount of blood tests will depend on the patient s age, weight and health, but is expected that blood will not be drawn more than twice a month. Patients will also undergo bone marrow biopsy aspirate (as described above) twice a year. Patients will be followed once a year indefinitely to evaluate the long-term effects of therapy.

Key facts

Study ID: NCT00018018
Run by: National Human Genome Research Institute (NHGRI)
People needed: 8
Starts: 2001-06-20
Expected to finish: 2014-09-17
Last updated by the study team: 2019-12-12

Who can join

Age: 0 and older. Sex: any. Healthy volunteers: not accepted.

You may not qualify if…

Age:
a. Age less than 1 month
Hematologic:
Anemia (hemoglobin less than 10.5 mg/dl, for subjects 2 years of age or less or hemoglobin less than 11.5 mg/dl for subjects older than 2 years of age in the presence of normal iron studies).
Neutropenia
i. absolute granulocyte count <500/mm (3) or
ii. absolute granulocyte count 500-999/mm (3) (ages 1-12 months) or 500-1,499/mm (3) for ages >1 year) and bone marrow studies showing myelodysplasia or other gross abnormalities.
c. Thrombocytopenia (platelet count less than 150,000 mm(3) at any age)
d. PT or PTT greater than 2 times normal.
e. Cytogenic abnormalities on peripheral blood.
Infectious:
a. Evidence of active opportunistic infection or infection with HIV-1, hepatitis B, CMV or parvovirus B19 by DNA PCR at time of assessment.
Pulmonary:
Resting O2 saturation by pulse oximetry less than 95%.
Chest X-ray indicating active or progressive pulmonary disease.
Cardiac:
Abnormal electrocardiogram (EKG) indicating cardiac pathology.
Uncorrected congenital cardiac malformation.
Active cardiac disease, including clinical evidence of congestive heart failure, cyanosis, or hypotension.
Neurologic:
Significant neurologic abnormality by examination.
Uncontrolled seizure disorder.
Renal:
Renal insufficiency: for pediatric patients serum creatinine greater than or equal to 1.2 mg/dl, or greater than or equal to 3+ proteinuria, for adults values at grades greater than or equal to of the NCI Common Toxicity Criteria (CTC).
Abnormal serum sodium, potassium, calcium, magnesium, phosphate at grade III or IV by DAIDS Toxicity Scale or NCI CTC.

Where it is running

National Institutes of Health Clinical Center, 9000 Rockville Pike — Bethesda, Maryland, United States

Full record on ClinicalTrials.gov

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