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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Treatment of SCID Due to ADA Deficiency With Autologous Cord Blood or Bone Marrow CD34+ Cells Transduced With a Human ADA Gene

Brief Summary:

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

Detailed Summary: This is a clinical gene transfer study that aims to verify the safety and efficacy of the use of retroviral vectors to introduce the human adenosine deaminase (ADA) gene into the hematopoietic progenitors of patients affected with severe combined immunodeficiency due to ADA deficiency. In addition, this protocol will examine the effects of the ADA gene transfer on the immune system of treated patients. Patients with ADA deficiency and ineligible for matched sibling allogeneic bone marrow transplantation are eligible to participate to the study. To increase engraftment and selective advantage of gene-corrected cells, busulfan will be used as cytoreduction agent and enzyme replacement (PEG-ADA) therapy will be discontinued. CD34+ hematopoietic progenitors will be isolated from the patient bone marrow or cord blood, exposed to retroviral vector-mediated gene transfer and reinfused into the patient through a peripheral vein. Clinical, immunological and molecular follow-up studies will assess safety, toxicity, and efficacy of the procedure.
Sponsor: National Human Genome Research Institute (NHGRI)

Current Primary Outcome:

Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: June 27, 2001
Date Started: June 20, 2001
Date Completion:
Last Updated: April 19, 2017
Last Verified: September 17, 2014