Severe Combined Immunodeficiency Syndrome Clinical Trial
Official title:
Treatment of SCID Due to ADA Deficiency With Autologous Cord Blood or Bone Marrow CD34+ Cells Transduced With a Human ADA Gene
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.
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. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00599781 -
Gene Therapy for ADA-SCID
|
Phase 1/Phase 2 |