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Targeting Acute Myeloid Leukemia Immunosuppressive Microenvironment by combinedIDO1 Inhibition and PD-1 Blockade

NCT06874257 · Status: RECRUITING · Type: OBSERVATIONAL · Enrollment: 20

Last updated 2025-03-13

No results posted yet for this study

Summary

The combination of azacitidine and venetoclax is currently considered a therapeutic strategy innovative in AML through the addition of new compounds (triplet therapies), including inhibitors of the immune checkpoint inhibitors. Despite strong motivation, the clinical results of these approaches have been disappointing overall. The mechanisms leading to treatment failure of immunotherapies in AML are poorly elucidated as the effects on the AML microenvironment induced by basic azactidine and venetoclax therapy are largely unknown. In particular, the activity of the IDO1 enzyme as a potential mechanism of microenvironment resistance has been scarcely studied. The products of the IDO1-catalysed pathway activate the signalling of the AHR in mesenchymal stem cells and enhance their immunosuppressive effects, including the ability to reprogram the phenotype of M1/M2 macrophages. Furthermore, activation of the AHR by by products of the IDO1 pathway kinurenine-promotes tolerogenic dendritic cells and the generation of regulatory T cells. Based on this rationale, TALETE-2023 will aim to analyse the leukaemia immune microenvironment through multiomics (epigenomics transcriptomics, proteomics, metabolomics) and assess its contribution to the effect of the combination of azacitidine and venetoclax.

Conditions

  • AML (Acute Myelogenous Leukemia)

Interventions

BIOLOGICAL

Laboratory tests and in vitro studies

Cell models, co-culture condition set-up and functional validation, Single-cell RNA sequencing and NGS, Metabolomics analysis, metabolomics validation and intracellular metabolomics analysis, Metabolic ImmunoProfiling and epigenetic profile, CyTOF immune and signaling profiling, Monocyte, macrophages and MSCs in vitro assays.

Sponsors & Collaborators

  • IRCCS Azienda Ospedaliero-Universitaria di Bologna

    lead OTHER

Principal Investigators

  • Antonio Curti, MD · IRCCS Azienda Ospedaliero-Universitaria di Bologna

Eligibility

Min Age
18 Years
Sex
ALL
Healthy Volunteers
Yes

Timeline & Regulatory

Start
2024-04-17
Primary Completion
2025-10-31
Completion
2026-10-31

Countries

  • Italy

Study Locations

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Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06874257 on ClinicalTrials.gov