Treatment With Immunological Checkpoint Inhibitors of HIV-infected Subjects With Cancer (PembroHIV)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03767465|
Recruitment Status : Completed
First Posted : December 6, 2018
Last Update Posted : January 18, 2020
|Condition or disease|
|HIV Infection Cancer|
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.
|Study Type :||Observational|
|Actual Enrollment :||1 participants|
|Official Title:||Treatment With Immunological Checkpoint Inhibitors of HIV-infected Subjects With Cancer|
|Actual Study Start Date :||October 26, 2018|
|Actual Primary Completion Date :||March 18, 2019|
|Actual Study Completion Date :||October 11, 2019|
HIV-infected subjects with advanced melanoma or other oncological conditions in which the use of immunological checkpoint inhibitors is clinically indicated
- 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
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
|Hospital Universitari Germans Trias i Pujol|
|Badalona, Barcelona, Spain, 08916|
|Principal Investigator:||Javier Martinez-Picado, PhD||IrsiCaixa|