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Sponsored by: |
National Human Genome Research Institute (NHGRI) |
Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00018018 |
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.
Condition | Intervention | Phase |
Severe Combined Immunodeficiency Syndrome |
Drug: CD34+ cells transduced with ADA retrovir |
Phase I |
Genetics Home Reference related topics: | adenosine deaminase deficiency X-linked severe combined immunodeficiency |
Drug Information available for: | Zidovudine Adenosine |
Study Type: | Interventional |
Study Design: | Treatment |
Official Title: | Treatment of SCID Due to ADA Deficiency With Autologous Cord Blood or Bone Marrow CD34+ Cells Transduced With a Human ADA Gene |
Estimated Enrollment: | 10 |
Study Start Date: | June 2001 |
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. A secondary aim of this research study is to compare two different retroviral vectors for their ability to provide genetic correction of hematopoietic progenitors and induce T cell development. Finally, 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, divided into two aliquots, separately exposed to two retroviral vectors 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.
Ages Eligible for Study: | 6 Months and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Patients will be enrolled into this study if they fulfill the following three criteria:
A. Patients of age greater than 6 months with a diagnosis of ADA-deficiency based on:
Confirmed absence (less than 3% of normal levels) of ADA enzymatic activity in peripheral blood or (for neonates) umbilical cord erythrocytes and/or leukocytes, or in cultured fetal cells derived from either chorionic villus biopsy or amniocentesis, prior to institution of enzyme replacement therapy.
AND
Evidence of severe combined immunodeficiency based on either:
Family history of first order relative with ADA deficiency and clinical and laboratory evidence of severe immunologic deficiency
OR
Evidence of severe immunologic deficiency in subject based on lymphopenia (absolute lymphocyte count less than 200) or severely decreased T lymphocyte blastogenic responses to phytohemagglutinin (cpm less than 5,000) prior to institution of immune restorative therapy
OR
B. Patients ineligible for allogeneic (matched sibling) bone marrow transplantation (BMT) based on:
Absence of a medically eligible HLA-identical sibling with normal immune function who may serve as an allogenic bone marrow donor
OR
Election by the parents or the adult patients to forgo allogeneic BMT in favor of PEG-ADA enzyme therapy after being invited to discuss alternative treatment options with a physician not connected with the protocol.
C. Written informed consent according to guidelines of the NHGRI IRB, NIH or the Committee on Clinical Investigations (CCI) at Children's Hospital Los Angeles (CHLA).
This study is also open to delayed/late onsent ADA-deficient patients who fulfill the criteria A, B.1, and C and who are not receiving PEG-ADA treatment after being invited to discuss all alternative treatment options with a physician not connected with the protocol.
EXCLUSION CRITERIA:
Age:
a. Age less than 6 months
Hematologic:
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:
Cardiac:
Neurologic:
Renal:
Hepatic/Gl:
Oncologic:
a. Evidence of active malignant disease.
General:
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: TTY | 1-866-411-1010 |
United States, California | |||||
Childrens Hospital, Los Angeles | Recruiting | ||||
Los Angeles, California, United States, 90054-0700 | |||||
United States, Maryland | |||||
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting | ||||
Bethesda, Maryland, United States, 20892 |
NIH Clinical Center Detailed Web Page 
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Study ID Numbers: | 010189, 01-HG-0189 |
First Received: | June 27, 2001 |
Last Updated: | August 19, 2008 |
ClinicalTrials.gov Identifier: | NCT00018018 |
Health Authority: | United States: Federal Government |
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