HIV InfectionsPhase 1NCT00110578
Safety and Effectiveness of Immunotherapy With Autologous HIV-Specific CD8 Cells in HIV Infected Adults
A Phase 1 study testing Adoptive transfer of HIV-specific CD8+ T cells and Aldesleukin in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites in United States.
Trial summary
Effective, suppressive treatment for HIV infected patients can be a major challenge because HIV progressively destroys their immune systems. CD8 cells isolated from a patient's blood and grown in large numbers in the laboratory may increase a patient's immune system response to HIV. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- HIV Infections
- What is being tested?
- Adoptive transfer of HIV-specific CD8+ T cells and Aldesleukin
- Type of treatment
- Surgery or procedure
- How many people
- 24 participants
- Where
- 2 sitesUnited States
- Study dates
- Sep 1998to Apr 2005
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HIV infected
- CD4 count greater than 200 cells/mm3 at study entry
- Absolute neutrophil count greater than 1000 cells/mm3
- Willing to take Pneumocystis prophylaxis, if indicated
- Willing to comply with study requirements
- Willing to forgo other experimental therapy during the 26-week study period
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- Willing to use acceptable forms of contraception
- Currently receiving treatment with an FDA-approved or expanded access antiretroviral agent (or combinations thereof) at a stable dose for at least 24 weeks prior to study entry
- Have not received antiretroviral therapy for 6 months prior to study entry
Who cannot join
- Treatment with other immunomodulatory therapies (interferon, HIV vaccines, intravenous immunoglobulin), pentoxifylline, cancer chemotherapy, radiation therapy, or other investigational agents
- Past or present infection with mycobacterium avium complex, toxoplasmosis, cryptococcus, or cytomegalovirus (including retinitis)
- Active opportunistic infection at study entry or serious systemic infection requiring chronic maintenance or suppressive therapy
- Lymphoma, symptomatic visceral Kaposi's sarcoma, or any malignancy expected to require systemic therapy
- Serious psychological or emotional disorder that would affect ability to comply with study requirements or that would be exacerbated by protocol participation
- Alcohol or drug use, abuse, or dependence that, in the opinion of the investigator, would interfere with the study
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- Estimated life expectancy of less than 4 months
- Abnormal neurocognitive examination
- Significant abnormality on electrocardiogram or chest radiograph
- Inability to generate CD8+ HIV-specific cytotoxic T cell clones
- Previously treated in FHCRC Protocol #827.1
- Pregnancy or breastfeeding
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Fred Hutchinson Cancer Research Center
Seattle, Washington, 98109
University of Washington (UW)
Seattle, Washington, 98122
About this study
Official title: Safety and Antiviral Efficacy of Cellular Adoptive Immunotherapy With Autologous CD8+ HIV-Specific Cytotoxic T Cells Combined With Interleukin-2 For HIV Seropositive Individuals
Effective, suppressive treatment for HIV infected patients can be a major challenge because HIV progressively destroys their immune systems. CD8 cells isolated from a patient's blood and grown in large numbers in the laboratory may increase a patient's immune system response to HIV. The purpose of this study is to determine if CD8 cells will provide effective antiviral activity against HIV when transplanted back in large numbers into HIV infected patients.
Study hypothesis: There are specific cells in the immune system that recognize and can kill HIV-infected cells.
Read the detailed description
The function of CD8 cells in the human body is to kill infected target cells, such as HIV infected cells. Recent data suggest that intravenous administration of HIV-specific CD8 cells is safe, augments host immunity, and mediates a dramatic reduction in circulating HIV-infected CD4 cells. However, the observed antiviral effects are transient, and HIV infected CD4 cells re-emerge as the number of self CD8 cells declines. Augmenting CD8 cell response to HIV by immunotherapy with CD8 cells may be a useful addition to drug therapy if the infused CD8 cells can survive long-term in vivo. Administration of interleukin-2 (also known as aldesleukin or IL-2), a naturally occurring cytokine, has been proposed as a way to maintain the number of CD8 cells. This study will evaluate the safety and efficacy of immunotherapy with HIV-specific CD8 cells in HIV infected patients. Additionally, this study will determine if aldesleukin injections improve the persistence of self CD8 transplants and the duration of antiviral activity without severe toxicity.
This study will last 18 months. CD8 cells will be isolated from the blood of HIV infected patients; the cells will be allowed to multiply in the laboratory, and patients will receive back their CD8 cells. Patients will receive up to 3 infusions of self CD8 cells. On Day 0, patients will receive their first infusion of CD8 cells. On Day 7, patients will receive their second infusion of CD8 cells; this infusion will be followed by 14 days of aldesleukin administered daily by injection under the skin. Patients with less than a Grade 2 toxicity will receive a third infusion of CD8 cells; this infusion will be followed by 21 days of aldesleukin.
- Conditions
- HIV Infections
- Being tested
- Adoptive transfer of HIV-specific CD8+ T cells, Aldesleukin
- Keywords
- Treatment Naive, Treatment Experienced
- Medical subject headings
- HIV Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adoptive transfer of HIV-specific CD8+ T cellsProcedure or surgery
AldesleukinDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety of administering CD8+ HIV-specific CTL clones followed by subcutaneous IL-2 (Proleukin, Chiron) daily for up to 21 days
To identify a regimen of IL-2 that will improve the in vivo persistence and function of adoptively transferred CD8+ HIV-specific CTL
Secondary outcomes (2)
To determine whether the administration of IL-2 prolongs the antiviral activity of transferred CD8+ HIV-specific CTL
To determine if IL-2 promotes the accumulation of adoptively transferred CD8+ HIV-specific CTL in lymph nodes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2005 (estimated)
- Study startSep 1998
- Study completionApr 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HIV InfectionsStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
- 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
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Investigators
- Stanley Riddell, MD, Principal investigator, Fred Hutchinson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00110578
- Sponsor's protocol ID
- 5U01AI054334-02
- Other IDs
- AI54334
- Status last verified
- Jul 2007
- First submitted
- 10 May 2005
- Last updated
- 8 Aug 2008
- Results posted
- No
Publications
Chapuis AG, Casper C, Kuntz S, Zhu J, Tjernlund A, Diem K, Turtle CJ, Cigal ML, Velez R, Riddell S, Corey L, Greenberg PD. HIV-specific CD8+ T cells from HIV+ individuals receiving HAART can be expanded ex vivo to augment systemic and mucosal immunity in vivo. Blood. 2011 May 19;117(20):5391-402. doi: 10.1182/blood-2010-11-320226. Epub 2011 Mar 21.
PubMed 21422474
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Antiviral Efficacy of Cellular Adoptive Immunotherapy With Autologous CD8+ HIV-Specific Cytotoxic T Cells Combined With Interleukin-2 For HIV Seropositive Individuals
- ClinicalTrials.gov ID
- NCT00110578
- Acronym / sponsor ID
- 5U01AI054334-02
- Conditions
- HIV Infections
- Keywords
- Treatment Naive, Treatment Experienced
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- Sep 1998
- Study completion
- Apr 2005
- First posted
- 11 May 2005 (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.
Effective, suppressive treatment for HIV infected patients can be a major challenge because HIV progressively destroys their immune systems. CD8 cells isolated from a patient's blood and grown in large numbers in the laboratory may increase a patient's immune system response to HIV. The purpose of this study is to determine if CD8 cells will provide effective antiviral activity against HIV when transplanted back in large numbers into HIV infected patients.
Study hypothesis: There are specific cells in the immune system that recognize and can kill HIV-infected cells.
Detailed description
The function of CD8 cells in the human body is to kill infected target cells, such as HIV infected cells. Recent data suggest that intravenous administration of HIV-specific CD8 cells is safe, augments host immunity, and mediates a dramatic reduction in circulating HIV-infected CD4 cells. However, the observed antiviral effects are transient, and HIV infected CD4 cells re-emerge as the number of self CD8 cells declines. Augmenting CD8 cell response to HIV by immunotherapy with CD8 cells may be a useful addition to drug therapy if the infused CD8 cells can survive long-term in vivo. Administration of interleukin-2 (also known as aldesleukin or IL-2), a naturally occurring cytokine, has been proposed as a way to maintain the number of CD8 cells. This study will evaluate the safety and efficacy of immunotherapy with HIV-specific CD8 cells in HIV infected patients. Additionally, this study will determine if aldesleukin injections improve the persistence of self CD8 transplants and the duration of antiviral activity without severe toxicity.
This study will last 18 months. CD8 cells will be isolated from the blood of HIV infected patients; the cells will be allowed to multiply in the laboratory, and patients will receive back their CD8 cells. Patients will receive up to 3 infusions of self CD8 cells. On Day 0, patients will receive their first infusion of CD8 cells. On Day 7, patients will receive their second infusion of CD8 cells; this infusion will be followed by 14 days of aldesleukin administered daily by injection under the skin. Patients with less than a Grade 2 toxicity will receive a third infusion of CD8 cells; this infusion will be followed by 21 days of aldesleukin.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- HIV infected
- CD4 count greater than 200 cells/mm3 at study entry
- Absolute neutrophil count greater than 1000 cells/mm3
- Willing to take Pneumocystis prophylaxis, if indicated
- Willing to comply with study requirements
Key exclusion criteria (12 listed)
- Treatment with other immunomodulatory therapies (interferon, HIV vaccines, intravenous immunoglobulin), pentoxifylline, cancer chemotherapy, radiation therapy, or other investigational agents
- Past or present infection with mycobacterium avium complex, toxoplasmosis, cryptococcus, or cytomegalovirus (including retinitis)
- Active opportunistic infection at study entry or serious systemic infection requiring chronic maintenance or suppressive therapy
- Lymphoma, symptomatic visceral Kaposi's sarcoma, or any malignancy expected to require systemic therapy
- Serious psychological or emotional disorder that would affect ability to comply with study requirements or that would be exacerbated by protocol participation
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 |
|---|---|---|
| Adoptive transfer of HIV-specific CD8+ T cells | Procedure or surgery | – |
| Aldesleukin | Drug | – |
Primary outcome
To determine the safety of administering CD8+ HIV-specific CTL clones followed by subcutaneous IL-2 (Proleukin, Chiron) daily for up to 21 days
To identify a regimen of IL-2 that will improve the in vivo persistence and function of adoptively transferred CD8+ HIV-specific CTL
2 secondary outcomes
To determine whether the administration of IL-2 prolongs the antiviral activity of transferred CD8+ HIV-specific CTL
To determine if IL-2 promotes the accumulation of adoptively transferred CD8+ HIV-specific CTL in lymph nodes
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 Aug 2008.
- Derived from this study: PubMed 21422474Chapuis AG, Casper C, Kuntz S, Zhu J, Tjernlund A, Diem K, Turtle CJ, Cigal ML, Velez R, Riddell S, Corey L, Greenberg PD. HIV-specific CD8+ T cells from HIV+ individuals receiving HAART can be expanded ex vivo to augment systemic and mucosal immunity in vivo. Blood. 2011 May 19;117(20):5391-402. doi: 10.1182/blood-2010-11-320226. Epub 2011 Mar 21.
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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.
Stanley Riddell, MD principal investigator
Fred Hutchinson Cancer Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Adoptive transfer of HIV-specific CD8+ T cells and Aldesleukin in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 2 sites 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 12 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 Aug 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
What does the primary outcome measure?
To determine the safety of administering CD8+ HIV-specific CTL clones followed by subcutaneous IL-2 (Proleukin, Chiron) daily for up to 21 days. The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00110578, which also lists 1 linked publication.
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 Aug 2008.