Treatment With Immunological Checkpoint Inhibitors of HIV-infected Subjects With Cancer

Cancer Clinical Trial

— PembroHIV  

Official title:

Treatment With Immunological Checkpoint Inhibitors of HIV-infected Subjects With Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03767465
• Other study ID #: PembroHIV
• Status: Completed
• Start date: October 26, 2018
• Est. completion date: October 11, 2019

Study information

• Verified date: January 2020
• Source: IrsiCaixa
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1
• Est. completion date: October 11, 2019
• Est. primary completion date: March 18, 2019
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer
• HIV Infection
• HIV Infections

Locations

Country	Name	City	State
Spain	Hospital Universitari Germans Trias i Pujol	Badalona	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
IrsiCaixa

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Quantification of total HIV DNA	Measurement of HIV viral latency by quantification of total HIV DNA in purified CD4+ T cells, using digital droplet PCR (ddPCR)	At the end of recruitment (up to one year after inclusion)
Primary	Quantification of cell-associated HIV RNA	Measurement of viral transcription by quantification of cell-associated unspliced HIV RNA in purified CD4+ T cells, using ddPCR	At the end of recruitment (up to one year after inclusion)
Primary	Quantification of ultrasensitive HIV viral load	Measurement of ultrasensitive viremia in plasma using single copy assay	At the end of recruitment (up to one year after inclusion)
Primary	Analysis of changes in HIV-specific cellular responses	Changes in the ability of Peripheral Blood Mononuclear Cells (PBMCs) to release Interferon gamma (IFN?) in response to viral antigen stimulation (ELISPOT assay).	At the end of recruitment (up to one year after inclusion)
Primary	Analysis of changes in immune-phenotype of cellular populations	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).	At the end of recruitment (up to one year after inclusion)
Primary	Analysis of changes in HIV inhibition capacity in vitro	Changes in the ex vivo ability of cluster of differentiation 8 (CD8)+ T cells to inhibit superinfected autologous CD4+ T cells (virus inhibition assay).	At the end of recruitment (up to one year after inclusion)
Primary	Supervision of changes on the standard blood analysis for oncologic follow-up	Blood analysis will be revised for oncologic follow-up	At the end of recruitment (up to one year after inclusion)
Primary	Analysis of changes in imaging of the oncological focus	Positron Emission Tomography (PET) scan will be analyzed for oncologic follow-up	At the end of recruitment (up to one year after inclusion)