Ignite Creation Date:
2024-05-05 @ 10:00 AM
Last Modification Date:
2024-10-26 @ 9:02 AM
Study NCT ID:
NCT00001353
Status:
COMPLETED
Last Update Posted:
2008-03-04
First Post:
1999-11-03
Brief Title:
Safety and Survival of Genetically Modified White Blood Cells in HIV-Infected Persons - A Study in Identical Twin Pairs
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
A Study of the Safety and Survival of the Adoptive Transfer of Genetically Marked Syngeneic Lymphocytes in HIV-Infected Identical Twins
Status:
COMPLETED
Status Verified Date:
2002-03
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 the safety of giving lymphocytes white blood cells containing a new gene to HIV-infected individuals and will determine how long the cells survive in the bloodstream Although the genetically altered cells will not directly benefit participants knowledge about the safety side effects and survival of these gene-marked cells in HIV-infected patients may lead to new treatment strategies
Identical twin pairs 18 years of age and older-one infected with HIV the other non-infected-may be eligible for this study Candidates will be screened with a medical history physical examination and blood tests
All participants will have a tetanus booster shot Non-infected twins will undergo a procedure called apheresis to collect white blood cells For this procedure whole blood is collected through a needle in an arm vein similar to donating blood The blood is separated it into its components by centrifugation spinning the white cells are removed and the rest of the blood is returned to the body either through the same needle or through another needle in the other arm The harvested white cells will be grown in culture for approximately 10 days to 2 weeks to increase their numbers up to 1000-fold A gene called NeoR which is derived from bacteria will be inserted into the cells and these gene-marked cells will be infused into the HIV-infected twin
HIV-infected twins will be admitted to the NIH Clinical Center for the first cell infusion The gene-marked cells will be infused over a 60-minute period through a plastic tube catheter placed in an arm vein or if a suitable arm vein cannot be found through a special catheter placed into a large vein in the neck or chest Vital signs temperature pulse blood pressure and breathing rate blood oxygen concentration and urine output will be monitored regularly for 24 hours Blood samples will be collected before and after the infusion to monitor for gene-marked cells Patients will be discharged the next day They will return to NIH daily the first week from Monday through Thursday to monitor for CD4 cell counts plasma viral burden p24 antigen levels HIV levels and the presence of the NeoR gene and then weekly for the next 5 weeks for these tests and others to monitor blood and urine chemistry blood counts and immune function markers
If the NeoR gene cannot be detected after the first cell infusion the entire procedure donor apheresis gene marking and infusion of cells will be repeated twice-about once every 6 weeks If the first infusion was uncomplicated the second and third infusions may be done on an outpatient basis with monitoring for 6 hours rather than 24 Six weeks after the third infusion tests will be scheduled monthly for 6 months and then yearly for long-term follow-up
In addition to the above procedures patients with a baseline CD4 lymphocyte count less than 100 cells per cubic millimeter of blood will be asked to undergo apheresis periodically to obtain the most accurate results for determining how long the NeoR gene persists in the blood The procedure will be done weekly for the first 6 weeks after each infusion of cells then at week 8 and then every 4 weeks until the gene can no longer be detected in the lymphocytes The schedule may change but will not require more frequent apheresis
Identical twin pairs 18 years of age and older-one infected with HIV the other non-infected-may be eligible for this study Candidates will be screened with a medical history physical examination and blood tests
All participants will have a tetanus booster shot Non-infected twins will undergo a procedure called apheresis to collect white blood cells For this procedure whole blood is collected through a needle in an arm vein similar to donating blood The blood is separated it into its components by centrifugation spinning the white cells are removed and the rest of the blood is returned to the body either through the same needle or through another needle in the other arm The harvested white cells will be grown in culture for approximately 10 days to 2 weeks to increase their numbers up to 1000-fold A gene called NeoR which is derived from bacteria will be inserted into the cells and these gene-marked cells will be infused into the HIV-infected twin
HIV-infected twins will be admitted to the NIH Clinical Center for the first cell infusion The gene-marked cells will be infused over a 60-minute period through a plastic tube catheter placed in an arm vein or if a suitable arm vein cannot be found through a special catheter placed into a large vein in the neck or chest Vital signs temperature pulse blood pressure and breathing rate blood oxygen concentration and urine output will be monitored regularly for 24 hours Blood samples will be collected before and after the infusion to monitor for gene-marked cells Patients will be discharged the next day They will return to NIH daily the first week from Monday through Thursday to monitor for CD4 cell counts plasma viral burden p24 antigen levels HIV levels and the presence of the NeoR gene and then weekly for the next 5 weeks for these tests and others to monitor blood and urine chemistry blood counts and immune function markers
If the NeoR gene cannot be detected after the first cell infusion the entire procedure donor apheresis gene marking and infusion of cells will be repeated twice-about once every 6 weeks If the first infusion was uncomplicated the second and third infusions may be done on an outpatient basis with monitoring for 6 hours rather than 24 Six weeks after the third infusion tests will be scheduled monthly for 6 months and then yearly for long-term follow-up
In addition to the above procedures patients with a baseline CD4 lymphocyte count less than 100 cells per cubic millimeter of blood will be asked to undergo apheresis periodically to obtain the most accurate results for determining how long the NeoR gene persists in the blood The procedure will be done weekly for the first 6 weeks after each infusion of cells then at week 8 and then every 4 weeks until the gene can no longer be detected in the lymphocytes The schedule may change but will not require more frequent apheresis
Detailed Description:
This phase III pilot project will evaluate the survival tolerance safety and efficacy of infusions of activated gene marked syngeneic T lymphocytes obtained from HIV seronegative identical twins on the functional immune status of HIV infected twin recipients T cells from each seronegative twin will be obtained by periodic apheresis induced to polyclonal proliferation with anti-CD3 and rIL-2 stimulation transduced with distinctive neoR retroviral vectors and expanded 10-1000 fold in numbers during approximately 2 weeks of culture These marked T cells will then be infused into the seropositive twins and the survival of the uniquely marked T cell populations will be monitored by vector-specific PCR while the recipients functional immune status is monitored by standard in vitro and in vivo testing protocols A total of 3 cycles of treatment may be given at intervals of 6 weeks between infusions
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 |
|---|---|---|---|
| 93-I-0110 | None | None | None |