|
Home
Search
Study Topics
Glossary
|
![]() |
![]() |
|
![]() |
|
![]() |
|
![]() |
![]() |
![]() |
|
![]() |
![]() |
||||||||||||||||||||||||||||||||||||
| Sponsored by: |
National Human Genome Research Institute (NHGRI) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00001535 |
Purpose
This study will test the safety and effectiveness of genetically altered T lymphocytes (white blood cells of the immune system) in reducing viral load in patients infected with the human immunodeficiency virus (HIV). The lymphocytes will have two genes inserted into them; a laboratory-manufactured anti-HIV gene designed to inhibit HIV reproduction (either the RevTD or Rev-TD-antiTAR gene), and a "marker" gene that will show whether or not the inserted genes have gotten into the cells.
Identical twin pairs 18 years of age and older- one of whom is HIV-positive (infected with the human immunodeficiency virus) and the other HIV-negative (not infected) may be eligible for this study.
All participants will have a complete medical history and physical examination, blood tests and a tetanus booster shot, if indicated. The non HIV-infected twin will then undergo lymphapheresis to collect lymphocytes. In this procedure, whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The lymphocytes are then removed, and the red cells and plasma are returned to the donor, either through the same needle or through a second needle placed in the other arm.
The donor cells are grown in the laboratory for a few days, and then the new genes are inserted into them. The genetically altered cells are grown in the laboratory for several days until their numbers increase approximately a thousand-fold. They are then infused intravenously (through a vein) into the infected twin. These procedures-lymphapheresis, gene modification and infusion-will be repeated at approximately 2-month intervals up to four times.
Each lymphocyte infusion takes about 60 minutes. The patient's vital signs (temperature, pulse, blood pressure and breathing) are monitored frequently during the infusion and hourly for 4 hours after the infusion. Blood samples are taken the day of the infusion, 3 days later, and then weekly to monitor the gene-modified cells, immune status, viral activity, and other factors. These tests may be done less often as the study progresses and more is learned about the safety of the infusions. The infusions are done on an outpatient basis unless side effects require that they be done in the hospital with post-infusion monitoring for at least 24 hours.
Patients will be followed for long-term effects of treatment monthly for the first 3 months, once a month for the next 9 months and yearly from then on.
This study will contribute information about the use and side effects of gene therapy in HIV infection that may lead to new treatment strategies.
A potential direct benefit to HIV-infected individuals participating in this study is reduced viral load; in laboratory studies, the RevTD and Rev-TD-antiTAR genes have inhibited HIV spread in the test tube. However, this is an early phase of study, and the likelihood of receiving this benefit is unknown.
| Condition | Intervention | Phase |
|---|---|---|
|
Acquired Immunodeficiency Syndrome HIV Infection Kaposi's Sarcoma |
Drug: Syngeneic Lymphocytes (CD4+) Cultured with OKT3 (Ortho) and Interleukin-2 (Chiro |
Phase I |
| Study Type: | Interventional |
| Study Design: | Treatment, Safety Study |
| Official Title: | Gene Therapy for AIDS Using Retroviral Mediated Gene Transfer to Deliver HIV-1 Anti-Sense TAR and Transdominant Rev Protein Genes to Syngeneic Lymphocytes in HIV-1 Infected Identical Twins |
| Estimated Enrollment: | 48 |
| Study Start Date: | March 1996 |
| Estimated Study Completion Date: | March 2002 |
This phase I/II pilot study will evaluate the safety, relative survival, and potential efficacy of infusions of activated, genetically engineered, syngeneic CD4+ T lymphocytes obtained from HIV-1 seronegative identical twins. T cells from each seronegative twin will be obtained by apheresis, enriched for CD4+ cells, induced to polyclonal proliferation with anti-CD3 and rIL-2 stimulation, divided into aliquots which will then be individually transduced with a control retroviral vector and up to two additional retroviral vectors containing potentially therapeutic genes (antisense TAR and/or transdominant Rev). These engineered T cell populations will be expanded 10-1,000 fold in numbers during 1-2 weeks of culture, and then will be infused into the seropositive twins. The relative survival of the uniquely engineered 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 up to 4 cycles of treatment may be given using identical or different combinations of control and anti-HIV-1 retroviral vectors.
Eligibility| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
INCLUSION CRITERIA:
EXCLUSION CRITERIA (Donor and Recipient):
EXCLUSION CRITERIA (Donor):
Contacts and Locations
More Information
| Study ID Numbers: | 960051, 96-HG-0051 |
| Study First Received: | November 3, 1999 |
| Last Updated: | February 7, 2008 |
| ClinicalTrials.gov Identifier: | NCT00001535 History of Changes |
| Health Authority: | United States: Federal Government |
|
Intracellular Immunization Immune Based Therapy Ex Vivo Cell Processing |
Identical Twins HIV/AIDS Kaposi's Sarcoma |
|
Sexually Transmitted Diseases, Viral Acquired Immunodeficiency Syndrome Sarcoma, Kaposi Immunologic Deficiency Syndromes Muromonab-CD3 Kaposi Sarcoma Herpesviridae Infections Virus Diseases Neoplasms, Connective and Soft Tissue Soft Tissue Sarcomas |
Malignant Mesenchymal Tumor Analgesics, Non-Narcotic Interleukin-2 HIV Infections Sexually Transmitted Diseases Sarcoma DNA Virus Infections Peripheral Nervous System Agents Analgesics Retroviridae Infections |
|
Communicable Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Antineoplastic Agents Physiological Effects of Drugs Infection Neoplasms, Connective and Soft Tissue Pathologic Processes Sensory System Agents Therapeutic Uses Syndrome Neoplasms, Vascular Tissue Analgesics Retroviridae Infections RNA Virus Infections |
Neoplasms by Histologic Type Disease Immune System Diseases Sarcoma, Kaposi Acquired Immunodeficiency Syndrome Pharmacologic Actions Immunologic Deficiency Syndromes Herpesviridae Infections Virus Diseases Neoplasms Analgesics, Non-Narcotic HIV Infections Interleukin-2 Sexually Transmitted Diseases Lentivirus Infections |