NCT03240328

Brief 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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
40

participants targeted

Target at P50-P75 for phase_1

Timeline
56mo left

Started Oct 2017

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress65%
Oct 2017Dec 2030

First Submitted

Initial submission to the registry

May 21, 2017

Completed
3 months until next milestone

First Posted

Study publicly available on registry

August 7, 2017

Completed
2 months until next milestone

Study Start

First participant enrolled

October 4, 2017

Completed
6.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2023

Completed
7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2030

Expected
Last Updated

September 14, 2022

Status Verified

September 1, 2022

Enrollment Period

6.2 years

First QC Date

May 21, 2017

Last Update Submit

September 13, 2022

Conditions

HIV/AIDS

Keywords

CAR-T HIV therapyimmunotherapyfunction cure

Outcome Measures

Primary Outcomes (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

    6 Months

Secondary Outcomes (2)

  • HIV-1 reservoir

    6 Months

  • HIV viral load rebound time

    6 months

Other Outcomes (1)

  • HIV-specific immunity

    6 Months

Study Arms (1)

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.

Biological: CAR-T cells

Interventions

CAR-T cellsBIOLOGICAL

HIV-1 specific chimeric antigen receptor cells

CAR-T therapy

Eligibility Criteria

Age18 Years - 60 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Guangzhou 8th People's Hospital

Guangzhou, Guangdong, 510060, China

RECRUITING

Related Publications (14)

  • 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.

    PMID: 23527958BACKGROUND

  • 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.

    PMID: 22160384BACKGROUND

  • 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.

    PMID: 25319501BACKGROUND

  • 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.

    PMID: 26962747BACKGROUND

  • 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.

    PMID: 22087695BACKGROUND

  • 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.

    PMID: 1900456BACKGROUND

  • 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.

    PMID: 24074590BACKGROUND

  • 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.

    PMID: 24307574BACKGROUND

  • 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.

    PMID: 25138734BACKGROUND

  • 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.

    PMID: 26050990BACKGROUND

  • 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.

    PMID: 25878112BACKGROUND

  • 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: 24329793BACKGROUND

  • 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: 27535056RESULT

  • 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.

    PMID: 34375315DERIVED

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

HIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune System Diseases

Intervention Hierarchy (Ancestors)

Adoptive TransferImmunization, PassiveImmunizationImmunotherapyImmunomodulationBiological TherapyTherapeuticsImmunologic TechniquesInvestigative Techniques

Study Officials

  • Cai Weiping, Bachelor

    Guangzhou 8th People's Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Li Linghua, Doctor

CONTACT

020-83710825llheliza@126.com

Cai Weiping, Bachelor

CONTACT

020-83710816gz8hcwp@126.com

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: No control.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Vice Chief physician

Study Record Dates

First Submitted

May 21, 2017

First Posted

August 7, 2017

Study Start

October 4, 2017

Primary Completion

December 31, 2023

Study Completion (Estimated)

December 31, 2030

Last Updated

September 14, 2022

Record last verified: 2022-09

Data Sharing

IPD Sharing
Will not share

Locations

CN(1)