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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.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

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.

Li Linghua, Doctor contact

020-83710825

llheliza@126.com

Cai Weiping, Bachelor contact

020-83710816

gz8hcwp@126.com

China1 site, 1 recruiting

  • Guangzhou 8th People's Hospital

    Guangzhou, Guangdong, 510060

    Linghua LI, doctor, 020-83710825, llheliza@126.com

    Recruiting

Other trials in China

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 groups in NCT03240328
Study groupRoleWhat they receive
CAR-T therapyExperimentalTransfusing 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.

  1. 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)

  1. HIV-1 reservoir

    To assay the HIV loads in the peripheral blood Mono-nuclear cells and plasma

    Measured: 6 Months

  2. 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.

  1. First posted7 Aug 2017
  2. Study start4 Oct 2017
  3. Primary completion31 Dec 2023 (estimated)
  4. Study completion31 Dec 2030 (estimated)

Resources

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)
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 23527958

  • Kochenderfer 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 22160384

  • Lee 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 25319501

  • Chimeric 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 26962747

  • Kochenderfer 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 22087695

  • Romeo 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 1900456

  • Sahu 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 24074590

  • Ni 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 24307574

  • MacLean 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 25138734

  • Zhen 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 26050990

  • Liu 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 25878112

  • Dotti 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 24329793

  • Liu 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 27535056

  • Liu 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

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.

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