Clinical Trials

MainTitle

Treatment With Immunological Checkpoint Inhibitors of HIV-infected Subjects With Cancer (PembroHIV)

This study is currently recruiting participants. (see Contacts and Locations)

Verified December 2018 by IrsiCaixa

Sponsor
IrsiCaixa


Information provided by (Responsible Party)
IrsiCaixa
ClinicalTrials.gov Identifier
NCT03767465

First received: December 3, 2018
Last updated: December 10, 2018
Last Verified: December 2018
History of Changes
Purpose

Purpose

It has been reported that peripheral and lymph node resident Cluster of Differentiation 4 (CD4)+ T cells expressing Programmed cell death protein 1 (PD-1) contribute to Human Immunodeficiency Virus (HIV) persistence during Antiretroviral Therapy (ART). In HIV-infected individuals, PD-1 expression on CD4+ T cells correlates with HIV disease progression, and loss of HIV-specific CD4+ T cell function can be reversed in vitro by PD-1 blockade. There are only a limited number of case reports describing the evolution of HIV-infected patients with concurrent oncological disease treated with immunological checkpoint inhibitors. However, this case provides very limited information on the effect of pembrolizumab on the HIV reservoir. Here, the investigators aim at describing changes in the HIV reservoir and in the HIV-specific immunity in HIV-infected patients on ART who receive immunological checkpoint inhibitors for the treatment of cancer, especially for metastatic melanoma.

Condition
HIV Infection
Cancer

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Other
Official Title: Treatment With Immunological Checkpoint Inhibitors of HIV-infected Subjects With Cancer

Further study details as provided by IrsiCaixa:

Primary Outcome Measures

  • Quantification of total HIV DNA [ Time Frame: At the end of recruitment (up to one year after inclusion) ]
    Measurement of HIV viral latency by quantification of total HIV DNA in purified CD4+ T cells, using digital droplet PCR (ddPCR)
  • Quantification of cell-associated HIV RNA [ Time Frame: At the end of recruitment (up to one year after inclusion) ]
    Measurement of viral transcription by quantification of cell-associated unspliced HIV RNA in purified CD4+ T cells, using ddPCR
  • Quantification of ultrasensitive HIV viral load [ Time Frame: At the end of recruitment (up to one year after inclusion) ]
    Measurement of ultrasensitive viremia in plasma using single copy assay
  • Analysis of changes in HIV-specific cellular responses [ Time Frame: At the end of recruitment (up to one year after inclusion) ]
    Changes in the ability of Peripheral Blood Mononuclear Cells (PBMCs) to release Interferon gamma (IFNγ) in response to viral antigen stimulation (ELISPOT assay).
  • Analysis of changes in immune-phenotype of cellular populations [ Time Frame: At the end of recruitment (up to one year after inclusion) ]
    Study of changes in multiple cell membrane markers related with cell function, including T-cell activation and proliferation, T-cell exhaustion, T-cell subpopulations and release of specific cytokines in response to HIV stimuli (multicolor flow cytometry).
  • Analysis of changes in HIV inhibition capacity in vitro [ Time Frame: At the end of recruitment (up to one year after inclusion) ]
    Changes in the ex vivo ability of cluster of differentiation 8 (CD8)+ T cells to inhibit superinfected autologous CD4+ T cells (virus inhibition assay).
  • Supervision of changes on the standard blood analysis for oncologic follow-up [ Time Frame: At the end of recruitment (up to one year after inclusion) ]
    Blood analysis will be revised for oncologic follow-up
  • Analysis of changes in imaging of the oncological focus [ Time Frame: At the end of recruitment (up to one year after inclusion) ]
    Positron Emission Tomography (PET) scan will be analyzed for oncologic follow-up

Biospecimen Retention: Samples With DNA
Criopreserved peripheral blood mononuclear cells (PBMCs) Frozen plasma

Estimated Enrollment: 3
Study Start Date: October 26, 2018
Estimated Study Completion Date: October 25, 2019
Estimated Primary Completion Date: October 25, 2019 (Final data collection date for primary outcome measure)

Arms
PembroHIV
HIV-infected subjects with advanced melanoma or other oncological conditions in which the use of immunological checkpoint inhibitors is clinically indicated

Detailed Description:

Long-lived latently infected resting CD4+ T cells are the main reason why current antiretroviral therapy (ART) is unable to cure HIV infection. Recent work has suggested that the expression of immune checkpoint markers, such as the programmed death-1 (PD1) or the cytotoxic T-lymphocyte antigen 4 (CTL-4), may play a role in viral persistence on ART via either suppression of virus transcription and/or reduced HIV-specific T cell activity, but the in vivo role of immune checkpoint markers in HIV persistence on ART is not clear.
Immunological checkpoint inhibitors are humanized monoclonal Immunoglobulin G (IgG) antibodies directed against several cell surface receptors, including PD-1 that inhibits binding of PD-1, expressed on activated T cells to its ligands PD-L1, overexpressed on certain cancer cells, and PD-L2, which is primarily expressed on antigen presenting cells. Activated PD-1 negatively regulates T-cell activation and plays a key role in tumor evasion from host immunity antigen presenting cells. Immunological checkpoint inhibitors can also target CTL-4, which is constitutively expressed in Treg cells but only upregulated in conventional T cells after activation, a phenomenon which is particularly notable in cancers. These drugs are used to treat oncology diseases, including metastatic melanoma, and have been associated with multiple changes in immune function thought to enhance antitumor T cell function.
This exploratory study will include HIV-infected subjects with advanced melanoma or other oncological conditions in which the use of immunological checkpoint inhibitors is clinically indicated. The study is conceptually observational as the patients will be in regular clinical treatment with immunological checkpoint inhibitors for oncological conditions.

Eligibility

Eligibility

Ages Eligible for Study: Child, Adult, Senior  
Sexes Eligible for Study: All  
Sampling Method: Non-Probability Sample  

Study Population

HIV-infected subjects with advanced melanoma or other oncological conditions in which the use of immunological checkpoint inhibitors is clinically indicated

Criteria

Inclusion Criteria:

  • HIV-infected subjects with advanced melanoma or other oncological conditions in which the use of immunological checkpoint inhibitors is clinically indicated


Exclusion Criteria:
  • None

contacts and locations

Contacts and Locations

Choosing to participate in a study is an important personal decision.Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03767465

Contacts

Contact:   Judith Dalmau, PhD 0034934656374 ext 161 jdalmau@irsicaixa.es

Locations

Spain
Hospital Universitari Germans Trias i Pujol Recruiting
Badalona, Barcelona, Spain, 08916
Contact: Judith Dalmau, PhD    0034934656374 ext 161    jdalmau@irsicaixa.es
Principal Investigator: Javier Martínez-Picado, PhD
Sub-Investigator: Judith Dalmau, PhD
Sub-Investigator: Cristina Gálvez

Sponsors and Collaborators

IrsiCaixa

Investigators

Principal Investigator: Javier Martinez-Picado, PhD IrsiCaixa
More Information

More Information


Responsible Party: IrsiCaixa  
ClinicalTrials.gov Identifier: NCT03767465   History of Changes  
Other Study ID Numbers: PembroHIV  
Study First Received: December 3, 2018  
Last Updated: December 10, 2018  
Individual Participant Data    
Plan to Share IPD: Undecided  

Studies a U.S. FDA-regulated Drug Product: No  
Studies a U.S. FDA-regulated Device Product: No  
Product Manufactured in and Exported from the U.S.: Yes  

Keywords provided by IrsiCaixa:

HIV
Cancer
Checkpoint inhibitors
HIV reservoir
Immunity

Additional relevant MeSH terms:
HIV Infections

ClinicalTrials.gov processed this data on August 16, 2019
This information is provided by ClinicalTrials.gov.