Clinical trial · Observational
Targeting Acute Myeloid Leukemia Immunosuppressive Microenvironment by combinedIDO1 Inhibition and PD-1 Blockade
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| AML (Acute Myelogenous Leukemia) | Acute Myeloid Leukemia | CURATED_BROADER | 0.80 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Laboratory tests and in vitro studies | Biological | — | UNRESOLVED |
Design
Arms and outcomes
Arms (1)
- label
- Patien with AML
- description
- The study will include untreated and newly diagnosed unfit-to-chemotherapy, adult AML patients candidate to receive the combination of venetoclax plus azacitidine according to standard clinical practice, and independently of the participation to the study. The patients will be enrolled at the time of disease diagnosis. For healthy donors, a total of 60 buffy coats will be collected in time period of 24 months. Patients who will not receive any treatment will be excluded from the study
- interventionNames
- Biological: Laboratory tests and in vitro studies
Primary outcomes (5)
- measure
- Pan-tissue AHR signature
- timeFrame
- At visit 1 (T1, diagnosis), and after the second cycle with azacitidine and venetoclax (T2, 2 months after treatment initiation)
- description
- Pan-tissue AHR signature levels will be measured by using iterative cycles of computational biology analyses and experimental validation (24). In particular, the levels of expression will be detected and a cutoff for differentially expressed genes will be set at log2 fold change.
- measure
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
Show eligibility criteria text
Inclusion Criteria: * Subject is ≥ 18 years of age * Subject has a new diagnosis of AML according to World Health Organization 2022 criteria * Subject is ineligible for intensive induction chemotherapy according to investigator assessment * Subject will undergo front-line treatment with azacitidine and venetoclax according to normal clinical practice * Subject providing signed written informed consent according to ICH/EU/GCP and national local laws For healthy donors: * Age ≥ 18 years * Subject providing signed written informed consent according to ICH/EU/GCP and national local laws Exclusion Criteria: For patients: * Subject has acute promyelocytic leukemia * Subject has known AML with central nervous system involvement * Subject has not initiated treatment with azacitidine and venetoclax For healthy donors: None
References
Publications (0)
Data not yet available