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

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ClinicalTrials.gov Identifier: NCT03767465
Recruitment Status : Recruiting
First Posted : December 6, 2018
Last Update Posted : December 12, 2018
Sponsor:
Information provided by (Responsible Party):
IrsiCaixa

Brief 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.

Condition or disease
HIV Infection Cancer

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.


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Study Type : Observational
Estimated Enrollment : 3 participants
Observational Model: Cohort
Time Perspective: Other
Official Title: Treatment With Immunological Checkpoint Inhibitors of HIV-infected Subjects With Cancer
Actual Study Start Date : October 26, 2018
Estimated Primary Completion Date : October 25, 2019
Estimated Study Completion Date : October 25, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

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



Primary Outcome Measures :
  1. 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)

  2. 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

  3. 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

  4. 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).

  5. 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).

  6. 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).

  7. 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

  8. 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


Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
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:


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03767465


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

Locations
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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
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Principal Investigator: Javier Martinez-Picado, PhD IrsiCaixa

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Responsible Party: IrsiCaixa
ClinicalTrials.gov Identifier: NCT03767465     History of Changes
Other Study ID Numbers: PembroHIV
First Posted: December 6, 2018    Key Record Dates
Last Update Posted: December 12, 2018
Last Verified: December 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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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:
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HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases