HIV/AIDSPhase 1NCT03240328
The Effect of Chimeric Antigen Receptor (CAR)-T Cell Therapy on the Reconstitution of HIV-specific Immune Function
A Phase 1 study testing CAR-T cells in people with HIV/AIDS, run by Guangzhou 8th People's Hospital at 1 site in China.
Trial summary
To study the safety and effectiveness of CAR-T Cell therapy on HIV patients whose plasma HIV has been successfully suppressed after cART, which is expected to enhance the res-constitution of HIV-specific immune function to assist the eradication of HIV reservoir. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- HIV/AIDS
- What is being tested?
- CAR-T cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 4 Oct 2017to 31 Dec 2030
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- HIV infection confirmed.
- Receiving cART more than 12 months.
- HIV viral-load < 50 copies/ml and CD4 cell count more than 350 cells/ul.
- Without serious liver, heart, liver and kidney diseases.
- The subjects know about the study and volunteer to attend the research and sign the informed consent.
Who cannot join
- With active HBV or HCV infection, or serious opportunistic infections.
- With serious chronic disease such like diabetes, the mental illness,et al
- History of suffering from pancreatitis during cART.
- Pregnant or breast-fed.
- With poor adherence.
- Unable to complete follow up.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Guangzhou 8th People's Hospital
Guangzhou, Guangdong, 510060
Linghua LI, doctor, 020-83710825, llheliza@126.com
About this study
Official title: The Effect of CAR-T Cell Therapy on the Reconstitution of HIV-specific Immune Function
To study the safety and effectiveness of CAR-T Cell therapy on HIV patients whose plasma HIV has been successfully suppressed after cART, which is expected to enhance the res-constitution of HIV-specific immune function to assist the eradication of HIV reservoir.
Read the detailed description
Despite the advent of combined antiretroviral therapy (cART), the persistence of viral reservoirs remains a major barrier to curing human immunodeficiency virus type 1 (HIV-1) infection. Recently, the shock and kill strategy, by which HIV-1 reservoirs could be eradicated following reactivation of latent HIV-1 by latency-reversing agents (LRAs), has been extensively practiced. It is important to reestablish virus-specific and reliable immune surveillance to eradicate the reactivated virus-harboring cells.the VC-CAR-T cells effectively induced the cytolysis of LRA-reactivated HIV-1-infected CD4 T lymphocytes isolated from infected individuals receiving successful cART. Our previous study demonstrated that the special features of genetically engineered CAR-T cells make them a particularly suitable candidate for therapeutic application in efforts to reach a functional HIV cure. In this clinical trial, we intend to study the safety and effectiveness of CAR-T Cell Therapy on HIV patients whose plasma HIV has been successfully suppressed after cART, by observing the adverse events, HIV-1 reservoir and the immune index.
- Conditions
- HIV/AIDS
- Being tested
- CAR-T cells
- Keywords
- CAR-T HIV therapy, immunotherapy, function cure
- Medical subject headings
- Acquired Immunodeficiency Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR-T cellsBiological
HIV-1 specific chimeric antigen receptor cells
| Study group | Role | What they receive |
|---|---|---|
| CAR-T therapy | Experimental | Transfusing CAR-T cells at least 1 million clone every time (once or twice) based on cART after attaining plasma HIV suppression (plasma HIV RNA <50 cp/ml) and CD4+ cell count more than 350 cells/ul over 1 year by cART without active HCV or HBV infection or opportunistic infections. If the candidates reach the criteria of discontinuing cART, they will stop cART and receive close observation. Once the plasma HIV viral load rebound to over 1000 cp/ml, they will restart cART immediately. Receives: Biological: CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-associated adverse events of CAR-T cell therapy
To observe the adverse events of VC-CAR-T cell therapy on HIV-infected patients during the clinical trial
Measured: 6 Months
Secondary outcomes (2)
HIV-1 reservoir
To assay the HIV loads in the peripheral blood Mono-nuclear cells and plasma
Measured: 6 Months
HIV viral load rebound time
To assay the HIV viral load rebound period after discontinuing cART
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2017
- Study start4 Oct 2017
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for HIV/AIDSStudies 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
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- No control.
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangzhou 8th People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Sun Yat-sen University
- Responsible party
- Principal investigator, Linghua LI, Guangzhou 8th People's Hospital
- Investigators
- Cai Weiping, Bachelor, Principal investigator, Guangzhou 8th People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03240328
- Sponsor's protocol ID
- 20170407V3
- Status last verified
- Sep 2022
- First submitted
- 21 May 2017
- Last updated
- 14 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013 Apr 18;368(16):1509-1518. doi: 10.1056/NEJMoa1215134. Epub 2013 Mar 25.
PubMed 23527958Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE, Maric I, Stetler-Stevenson M, Phan GQ, Hughes MS, Sherry RM, Yang JC, Kammula US, Devillier L, Carpenter R, Nathan DA, Morgan RA, Laurencot C, Rosenberg SA. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood. 2012 Mar 22;119(12):2709-20. doi: 10.1182/blood-2011-10-384388. Epub 2011 Dec 8.
PubMed 22160384Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN, Steinberg SM, Stroncek D, Tschernia N, Yuan C, Zhang H, Zhang L, Rosenberg SA, Wayne AS, Mackall CL. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015 Feb 7;385(9967):517-528. doi: 10.1016/S0140-6736(14)61403-3. Epub 2014 Oct 13.
PubMed 25319501Chimeric Antigen Receptor-Modified T Cells in Chronic Lymphoid Leukemia; Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia; Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. N Engl J Med. 2016 Mar 10;374(10):998. doi: 10.1056/NEJMx160005. No abstract available.
PubMed 26962747Kochenderfer JN, Rosenberg SA. Chimeric antigen receptor-modified T cells in CLL. N Engl J Med. 2011 Nov 17;365(20):1937-8; author reply 1938. doi: 10.1056/NEJMc1111004. No abstract available.
PubMed 22087695Romeo C, Seed B. Cellular immunity to HIV activated by CD4 fused to T cell or Fc receptor polypeptides. Cell. 1991 Mar 8;64(5):1037-46. doi: 10.1016/0092-8674(91)90327-u.
PubMed 1900456Sahu GK, Sango K, Selliah N, Ma Q, Skowron G, Junghans RP. Anti-HIV designer T cells progressively eradicate a latently infected cell line by sequentially inducing HIV reactivation then killing the newly gp120-positive cells. Virology. 2013 Nov;446(1-2):268-75. doi: 10.1016/j.virol.2013.08.002. Epub 2013 Sep 6.
PubMed 24074590Ni Z, Knorr DA, Bendzick L, Allred J, Kaufman DS. Expression of chimeric receptor CD4zeta by natural killer cells derived from human pluripotent stem cells improves in vitro activity but does not enhance suppression of HIV infection in vivo. Stem Cells. 2014 Apr;32(4):1021-31. doi: 10.1002/stem.1611.
PubMed 24307574MacLean AG, Walker E, Sahu GK, Skowron G, Marx P, von Laer D, Junghans RP, Braun SE. A novel real-time CTL assay to measure designer T-cell function against HIV Env(+) cells. J Med Primatol. 2014 Oct;43(5):341-8. doi: 10.1111/jmp.12137. Epub 2014 Aug 20.
PubMed 25138734Zhen A, Kamata M, Rezek V, Rick J, Levin B, Kasparian S, Chen IS, Yang OO, Zack JA, Kitchen SG. HIV-specific Immunity Derived From Chimeric Antigen Receptor-engineered Stem Cells. Mol Ther. 2015 Aug;23(8):1358-1367. doi: 10.1038/mt.2015.102. Epub 2015 Jun 8.
PubMed 26050990Liu L, Patel B, Ghanem MH, Bundoc V, Zheng Z, Morgan RA, Rosenberg SA, Dey B, Berger EA. Novel CD4-Based Bispecific Chimeric Antigen Receptor Designed for Enhanced Anti-HIV Potency and Absence of HIV Entry Receptor Activity. J Virol. 2015 Jul;89(13):6685-94. doi: 10.1128/JVI.00474-15. Epub 2015 Apr 15.
PubMed 25878112Dotti G, Gottschalk S, Savoldo B, Brenner MK. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev. 2014 Jan;257(1):107-26. doi: 10.1111/imr.12131.
PubMed 24329793Liu B, Zou F, Lu L, Chen C, He D, Zhang X, Tang X, Liu C, Li L, Zhang H. Chimeric Antigen Receptor T Cells Guided by the Single-Chain Fv of a Broadly Neutralizing Antibody Specifically and Effectively Eradicate Virus Reactivated from Latency in CD4+ T Lymphocytes Isolated from HIV-1-Infected Individuals Receiving Suppressive Combined Antiretroviral Therapy. J Virol. 2016 Oct 14;90(21):9712-9724. doi: 10.1128/JVI.00852-16. Print 2016 Nov 1.
PubMed 27535056Liu B, Zhang W, Xia B, Jing S, Du Y, Zou F, Li R, Lu L, Chen S, Li Y, Hu Q, Lin Y, Zhang Y, He Z, Zhang X, Chen X, Peng T, Tang X, Cai W, Pan T, Li L, Zhang H. Broadly neutralizing antibody-derived CAR T cells reduce viral reservoir in individuals infected with HIV-1. J Clin Invest. 2021 Oct 1;131(19):e150211. doi: 10.1172/JCI150211.
PubMed 34375315
Study at a glance
From the registry record, last updated by the sponsor on 14 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of CAR-T Cell Therapy on the Reconstitution of HIV-specific Immune Function
- ClinicalTrials.gov ID
- NCT03240328
- Acronym / sponsor ID
- 20170407V3
- Conditions
- HIV/AIDS
- Keywords
- CAR-T HIV therapy, immunotherapy, function cure
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Guangzhou 8th People's HospitalUniversity, hospital or other
- Collaborators
- Sun Yat-sen University
- Study start
- 4 Oct 2017 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 7 Aug 2017 (actual)
- 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.
To study the safety and effectiveness of CAR-T Cell therapy on HIV patients whose plasma HIV has been successfully suppressed after cART, which is expected to enhance the res-constitution of HIV-specific immune function to assist the eradication of HIV reservoir.
Detailed description
Despite the advent of combined antiretroviral therapy (cART), the persistence of viral reservoirs remains a major barrier to curing human immunodeficiency virus type 1 (HIV-1) infection. Recently, the shock and kill strategy, by which HIV-1 reservoirs could be eradicated following reactivation of latent HIV-1 by latency-reversing agents (LRAs), has been extensively practiced. It is important to reestablish virus-specific and reliable immune surveillance to eradicate the reactivated virus-harboring cells.the VC-CAR-T cells effectively induced the cytolysis of LRA-reactivated HIV-1-infected CD4 T lymphocytes isolated from infected individuals receiving successful cART. Our previous study demonstrated that the special features of genetically engineered CAR-T cells make them a particularly suitable candidate for therapeutic application in efforts to reach a functional HIV cure. In this clinical trial, we intend to study the safety and effectiveness of CAR-T Cell Therapy on HIV patients whose plasma HIV has been successfully suppressed after cART, by observing the adverse events, HIV-1 reservoir and the immune index.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- No control.
| Arm | Type | Receives |
|---|---|---|
| CAR-T therapy | Experimental | Biological: CAR-T cellsTransfusing CAR-T cells at least 1 million clone every time (once or twice) based on cART after attaining plasma HIV suppression (plasma HIV RNA <50 cp/ml) and CD4+ cell count more than 350 cells/ul over 1 year by cART without active HCV or HBV infection or opportunistic infections. If the candidates reach the criteria of discontinuing cART, they will stop cART and receive close observation. Once the plasma HIV viral load rebound to over 1000 cp/ml, they will restart cART immediately. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- HIV infection confirmed.
- Receiving cART more than 12 months.
- HIV viral-load < 50 copies/ml and CD4 cell count more than 350 cells/ul.
- Without serious liver, heart, liver and kidney diseases.
- The subjects know about the study and volunteer to attend the research and sign the informed consent.
Key exclusion criteria (6 listed)
- With active HBV or HCV infection, or serious opportunistic infections.
- With serious chronic disease such like diabetes, the mental illness,et al
- History of suffering from pancreatitis during cART.
- Pregnant or breast-fed.
- With poor adherence.
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 |
|---|---|---|
| CAR-T cellsHIV-1 specific chimeric antigen receptor cells | Biological | CAR-T therapy |
Primary outcome
Incidence of treatment-associated adverse events of CAR-T cell therapy
Time frame: 6 Months
To observe the adverse events of VC-CAR-T cell therapy on HIV-infected patients during the clinical trial
2 secondary outcomes
HIV-1 reservoir
Time frame: 6 Months
HIV viral load rebound time
Time frame: 6 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Sep 2022.
- Background: PubMed 23527958Grupp SA, Kalos M, Barrett D, Aplenc R, Porter DL, Rheingold SR, Teachey DT, Chew A, Hauck B, Wright JF, Milone MC, Levine BL, June CH. Chimeric antigen receptor-modified T cells for acute lymphoid leukemia. N Engl J Med. 2013 Apr 18;368(16):1509-1518. doi: 10.1056/NEJMoa1215134. Epub 2013 Mar 25.
- Background: PubMed 22160384Kochenderfer JN, Dudley ME, Feldman SA, Wilson WH, Spaner DE, Maric I, Stetler-Stevenson M, Phan GQ, Hughes MS, Sherry RM, Yang JC, Kammula US, Devillier L, Carpenter R, Nathan DA, Morgan RA, Laurencot C, Rosenberg SA. B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. Blood. 2012 Mar 22;119(12):2709-20. doi: 10.1182/blood-2011-10-384388. Epub 2011 Dec 8.
- Background: PubMed 25319501Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN, Steinberg SM, Stroncek D, Tschernia N, Yuan C, Zhang H, Zhang L, Rosenberg SA, Wayne AS, Mackall CL. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015 Feb 7;385(9967):517-528. doi: 10.1016/S0140-6736(14)61403-3. Epub 2014 Oct 13.
- Background: PubMed 26962747Chimeric Antigen Receptor-Modified T Cells in Chronic Lymphoid Leukemia; Chimeric Antigen Receptor-Modified T Cells for Acute Lymphoid Leukemia; Chimeric Antigen Receptor T Cells for Sustained Remissions in Leukemia. N Engl J Med. 2016 Mar 10;374(10):998. doi: 10.1056/NEJMx160005. No abstract available.
- Background: PubMed 22087695Kochenderfer JN, Rosenberg SA. Chimeric antigen receptor-modified T cells in CLL. N Engl J Med. 2011 Nov 17;365(20):1937-8; author reply 1938. doi: 10.1056/NEJMc1111004. No abstract available.
- Background: PubMed 1900456Romeo C, Seed B. Cellular immunity to HIV activated by CD4 fused to T cell or Fc receptor polypeptides. Cell. 1991 Mar 8;64(5):1037-46. doi: 10.1016/0092-8674(91)90327-u.
- Background: PubMed 24074590Sahu GK, Sango K, Selliah N, Ma Q, Skowron G, Junghans RP. Anti-HIV designer T cells progressively eradicate a latently infected cell line by sequentially inducing HIV reactivation then killing the newly gp120-positive cells. Virology. 2013 Nov;446(1-2):268-75. doi: 10.1016/j.virol.2013.08.002. Epub 2013 Sep 6.
- Background: PubMed 24307574Ni Z, Knorr DA, Bendzick L, Allred J, Kaufman DS. Expression of chimeric receptor CD4zeta by natural killer cells derived from human pluripotent stem cells improves in vitro activity but does not enhance suppression of HIV infection in vivo. Stem Cells. 2014 Apr;32(4):1021-31. doi: 10.1002/stem.1611.
- Background: PubMed 25138734MacLean AG, Walker E, Sahu GK, Skowron G, Marx P, von Laer D, Junghans RP, Braun SE. A novel real-time CTL assay to measure designer T-cell function against HIV Env(+) cells. J Med Primatol. 2014 Oct;43(5):341-8. doi: 10.1111/jmp.12137. Epub 2014 Aug 20.
- Background: PubMed 26050990Zhen A, Kamata M, Rezek V, Rick J, Levin B, Kasparian S, Chen IS, Yang OO, Zack JA, Kitchen SG. HIV-specific Immunity Derived From Chimeric Antigen Receptor-engineered Stem Cells. Mol Ther. 2015 Aug;23(8):1358-1367. doi: 10.1038/mt.2015.102. Epub 2015 Jun 8.
- Background: PubMed 25878112Liu L, Patel B, Ghanem MH, Bundoc V, Zheng Z, Morgan RA, Rosenberg SA, Dey B, Berger EA. Novel CD4-Based Bispecific Chimeric Antigen Receptor Designed for Enhanced Anti-HIV Potency and Absence of HIV Entry Receptor Activity. J Virol. 2015 Jul;89(13):6685-94. doi: 10.1128/JVI.00474-15. Epub 2015 Apr 15.
- Background: PubMed 24329793Dotti G, Gottschalk S, Savoldo B, Brenner MK. Design and development of therapies using chimeric antigen receptor-expressing T cells. Immunol Rev. 2014 Jan;257(1):107-26. doi: 10.1111/imr.12131.
- Individual participant dataSharing planned: No
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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.
Cai Weiping, Bachelor principal investigator
Guangzhou 8th People's Hospital
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 CAR-T cells in people with HIV/AIDS, run by Guangzhou 8th People's Hospital at 1 site in China.
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 5 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 14 Sep 2022. 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 China. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Li Linghua, Doctor (020-83710825, llheliza@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-associated adverse events of CAR-T cell therapy (time frame: 6 Months). 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 NCT03240328, which also lists 14 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 14 Sep 2022.