Ignite Creation Date:
2024-05-05 @ 11:23 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00018018
Status:
COMPLETED
Last Update Posted:
2019-12-12
First Post:
2001-06-27
Brief Title:
Gene Transfer Therapy for Severe Combined Immunodeficieny Disease SCID Due to Adenosine Deaminase ADA Deficiency
Sponsor:
National Human Genome Research Institute NHGRI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Treatment of SCID Due to ADA Deficiency With Autologous Cord Blood or Bone Marrow CD34 Cells Transduced With a Human ADA Gene
Status:
COMPLETED
Status Verified Date:
2014-09-17
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 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
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
Detailed Description:
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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01-HG-0189 | None | None | None |