Effect of Chidamide Combined With CAT-T or TCR-T Cell Therapy on HIV-1 Latent Reservoir

NCT03980691 | Completed Phase 1

• 1 other identifier: 20171126V1
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

To study the safety and effectiveness of the combination of Chidamide with Chimeric Antigen Receptor(CAR)-T or T cell receptor(TCR)-T cell therapy on HIV patients based on cART.

Conditions

HIV/AIDS

Keywords

Chidamide,CAR cell therapy,TCR cell therapy

Outcome Measures

Primary Outcomes (1)

• Incidence of treatment-associated adverse events

  To observe the adverse events of intervention n HIV-infected patients during the study.

  6 Months

Secondary Outcomes (1)

• HIV reservoir

  6 Months

Other Outcomes (1)

• HIV-specific immunity

  6 Months

Study Arms (2)

Chidamide combined with CAR-T or TCR-T cell therapy

EXPERIMENTAL

Receiving chidamide combined with CAR-T or TCR-T cell therapy based on 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.

Biological: Chidamide with CAR-T or TCR-T cell therapy

without intervention

NO INTERVENTION

Not receiving chidamide combined with CAR-T or TCR-T cell therapy but continuing 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.

Interventions

Chidamide with CAR-T or TCR-T cell therapy BIOLOGICAL

HIV-1 specific therapy

Chidamide combined with CAR-T or TCR-T cell therapy

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Guangzhou 8th People's Hospital: lead
• Sun Yat-sen University: collaborator

Study Sites (1)

Guangzhou 8th People's Hospital

Guangzhou, Guangdong, 510060, China

Location

Related Publications (6)

• 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.

  PMID: 24329793 BACKGROUND

• Liu C, Ma X, Liu B, Chen C, Zhang H. HIV-1 functional cure: will the dream come true? BMC Med. 2015 Nov 20;13:284. doi: 10.1186/s12916-015-0517-y.

  PMID: 26588898 BACKGROUND

• Kuai Q, Lu X, Qiao Z, Wang R, Wang Y, Ye S, He M, Wang Y, Zhang T, Wu H, Ren S, Yu Q. Histone deacetylase inhibitor chidamide promotes reactivation of latent human immunodeficiency virus by introducing histone acetylation. J Med Virol. 2018 Sep;90(9):1478-1485. doi: 10.1002/jmv.25207. Epub 2018 May 25.

  PMID: 29704439 BACKGROUND

• Yang W, Sun Z, Hua C, Wang Q, Xu W, Deng Q, Pan Y, Lu L, Jiang S. Chidamide, a histone deacetylase inhibitor-based anticancer drug, effectively reactivates latent HIV-1 provirus. Microbes Infect. 2018 Oct-Nov;20(9-10):626-634. doi: 10.1016/j.micinf.2017.10.003. Epub 2017 Nov 8.

  PMID: 29126877 BACKGROUND

• Kobayashi Y, Gelinas C, Dougherty JP. Histone deacetylase inhibitors containing a benzamide functional group and a pyridyl cap are preferentially effective human immunodeficiency virus-1 latency-reversing agents in primary resting CD4+ T cells. J Gen Virol. 2017 Apr;98(4):799-809. doi: 10.1099/jgv.0.000716. Epub 2017 Apr 27.

  PMID: 28113052 BACKGROUND

• 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.

  PMID: 27535056 RESULT

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

N-(2-amino-5-fluorobenzyl)-4-(N-(pyridine-3-acrylyl)aminomethyl)benzamide

Condition Hierarchy (Ancestors)

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Slow Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Weiping Cai, Bachelor

  Guangzhou 8th People's Hospital China, Guangdong

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice Chief physician

Model Details: The control arm includes HIV-infected patients without receiving cellar therapy combined with Chidamide whose HIV-1 has been successfully suppressed after cART.

Study Record Dates

• First Submitted: June 7, 2019
• First Posted: June 10, 2019
• Study Start: December 1, 2017
• Primary Completion: May 31, 2020
• Study Completion: May 31, 2020
• Last Updated: July 20, 2021

Record last verified: 2021-07

Locations

CN (1)