Acquired Immunodeficiency SyndromePhase 1NCT00001535
Twins Study of Gene Therapy for HIV Infection
A Phase 1 study testing Syngeneic Lymphocytes (CD4+) Cultured with OKT3 (Ortho) and Interleukin-2 (Chiro in people with Acquired Immunodeficiency Syndrome and HIV Infection, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Acquired Immunodeficiency Syndrome, HIV Infection, Kaposi's Sarcoma
- What is being tested?
- Syngeneic Lymphocytes (CD4+) Cultured with OKT3 (Ortho) and Interleukin-2 (Chiro
- How many people
- 48 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 1996to Mar 2002
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- An identical twin pair, one of whom is seropositive for HIV-1, the other twin seronegative, by standard ELISA and Western blot testing.
- Patients with Kaposi's sarcoma limited to the skin and/or mucous membranes are eligible for this study, but must not have received any systemic therapy for
- KS within 4 weeks prior to entry. The diagnosis of KS must have been confirmed by biopsy.
- Free from serious psychological or emotional illness and able to provide written informed consent.
- Anticipated survival greater than 3 months.
- 18 years of age or older.
Show all 9Show fewer
- Treatment with FDA-approved and/or expanded access antiretroviral agent(s) for patients with baseline CD4 counts below 500 cells/mm(3). Patients with baseline CD4 counts above 500 cells/mm(3) are eligible to receive cell therapy on this protocol, but must be treated with antiretroviral therapy if evidence of significant and persistent viral activation occurs in association with a cell infusion. "Significant and persistent viral activation" is defined as a 50 percent or greater increase above baseline in any virologic parameter for at least 2 consecutive weeks.
- Recipient's CD4 count greater than 50 cells/mm(3).
- Recipient and Donor willing to have samples stored and undergo HLA testing.
Who cannot join
- Lymphomas.
- Unwillingness to comply with current NIH Clinical Center guidelines concerning appropriate notification of all current sexual partners of an individual regarding his or her HIV-1 positive sero-status and the risk of transmission of HIV-1 infection.
- Recent history of substance abuse unless evidence is provided of an ongoing therapeutic intervention (i.e. medical therapy or counseling) to control such abuse.
- Pregnant at entry or unwillingness to practice barrier birth control or abstinence during the study.
- No experimental therapy within 4 weeks of study participation. Antiretroviral agents available on an FDA-sanctioned, expanded access basis are permitted.
- Untreated or inadequately treated medical condition (e.g., cardiopulmonary disease, acute infection) which, in the judgement of the Principal Investigator, precludes apheresis.
- Serologic positivity for Epstein Barr virus, Cytomegalovirus, Hepatitis B or Hepatitis C, if and only if the recipient twin tests seronegative for the corresponding virus.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Human Genome Research Institute (NHGRI)
Bethesda, Maryland, 20892
About this 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
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.
Read more
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.
Read the detailed description
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.
- Being tested
- Syngeneic Lymphocytes (CD4+) Cultured with OKT3 (Ortho) and Interleukin-2 (Chiro
- Keywords
- Intracellular Immunization, Immune Based Therapy, Ex Vivo Cell Processing, Identical Twins, HIV/AIDS, Kaposi's Sarcoma
- Medical subject headings
- Acquired Immunodeficiency Syndrome, HIV Infections, Sarcoma, Kaposi
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Syngeneic Lymphocytes (CD4+) Cultured with OKT3 (Ortho) and Interleukin-2 (ChiroDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startMar 1996
- Study completionMar 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Acquired Immunodeficiency SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Enrolment
- 48 participants
Sponsor and investigators
- Lead sponsor
- National Human Genome Research Institute (NHGRI)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001535
- Sponsor's protocol ID
- 960051
- Other IDs
- 96-HG-0051
- Status last verified
- Mar 2002
- First submitted
- 3 Nov 1999
- Last updated
- 8 Feb 2008
- Results posted
- No
Publications
VandenDriessche T, Chuah MK, Chiang L, Chang HK, Ensoli B, Morgan RA. Inhibition of clinical human immunodeficiency virus (HIV) type 1 isolates in primary CD4+ T lymphocytes by retroviral vectors expressing anti-HIV genes. J Virol. 1995 Jul;69(7):4045-52. doi: 10.1128/JVI.69.7.4045-4052.1995.
PubMed 7769662Morgan RA, Walker R. Gene therapy for AIDS using retroviral mediated gene transfer to deliver HIV-1 antisense TAR and transdominant Rev protein genes to syngeneic lymphocytes in HIV-1 infected identical twins. Hum Gene Ther. 1996 Jun 20;7(10):1281-306. doi: 10.1089/hum.1996.7.10-1281. No abstract available.
PubMed 8793552Lane HC, Zunich KM, Wilson W, Cefali F, Easter M, Kovacs JA, Masur H, Leitman SF, Klein HG, Steis RG, et al. Syngeneic bone marrow transplantation and adoptive transfer of peripheral blood lymphocytes combined with zidovudine in human immunodeficiency virus (HIV) infection. Ann Intern Med. 1990 Oct 1;113(7):512-9. doi: 10.7326/0003-4819-113-7-512.
PubMed 1975487
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00001535
- Acronym / sponsor ID
- 960051
- Keywords
- Intracellular Immunization, Immune Based Therapy, Ex Vivo Cell Processing, Identical Twins, HIV/AIDS, Kaposi's Sarcoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants
- Lead sponsor
- National Human Genome Research Institute (NHGRI)US National Institutes of Health
- Study start
- Mar 1996
- Study completion
- Mar 2002
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- An identical twin pair, one of whom is seropositive for HIV-1, the other twin seronegative, by standard ELISA and Western blot testing.
- Patients with Kaposi's sarcoma limited to the skin and/or mucous membranes are eligible for this study, but must not have received any systemic therapy for
- KS within 4 weeks prior to entry. The diagnosis of KS must have been confirmed by biopsy.
- Free from serious psychological or emotional illness and able to provide written informed consent.
- Anticipated survival greater than 3 months.
Key exclusion criteria (7 listed)
- Lymphomas.
- Unwillingness to comply with current NIH Clinical Center guidelines concerning appropriate notification of all current sexual partners of an individual regarding his or her HIV-1 positive sero-status and the risk of transmission of HIV-1 infection.
- Recent history of substance abuse unless evidence is provided of an ongoing therapeutic intervention (i.e. medical therapy or counseling) to control such abuse.
- Pregnant at entry or unwillingness to practice barrier birth control or abstinence during the study.
- No experimental therapy within 4 weeks of study participation. Antiretroviral agents available on an FDA-sanctioned, expanded access basis are permitted.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Syngeneic Lymphocytes (CD4+) Cultured with OKT3 (Ortho) and Interleukin-2 (Chiro | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2008.
- Background: PubMed 7769662VandenDriessche T, Chuah MK, Chiang L, Chang HK, Ensoli B, Morgan RA. Inhibition of clinical human immunodeficiency virus (HIV) type 1 isolates in primary CD4+ T lymphocytes by retroviral vectors expressing anti-HIV genes. J Virol. 1995 Jul;69(7):4045-52. doi: 10.1128/JVI.69.7.4045-4052.1995.
- Background: PubMed 8793552Morgan RA, Walker R. Gene therapy for AIDS using retroviral mediated gene transfer to deliver HIV-1 antisense TAR and transdominant Rev protein genes to syngeneic lymphocytes in HIV-1 infected identical twins. Hum Gene Ther. 1996 Jun 20;7(10):1281-306. doi: 10.1089/hum.1996.7.10-1281. No abstract available.
- Background: PubMed 1975487Lane HC, Zunich KM, Wilson W, Cefali F, Easter M, Kovacs JA, Masur H, Leitman SF, Klein HG, Steis RG, et al. Syngeneic bone marrow transplantation and adoptive transfer of peripheral blood lymphocytes combined with zidovudine in human immunodeficiency virus (HIV) infection. Ann Intern Med. 1990 Oct 1;113(7):512-9. doi: 10.7326/0003-4819-113-7-512.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Syngeneic Lymphocytes (CD4+) Cultured with OKT3 (Ortho) and Interleukin-2 (Chiro in people with Acquired Immunodeficiency Syndrome and HIV Infection, run by National Human Genome Research Institute (NHGRI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Feb 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001535, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Feb 2008.