Exploring Disease Immunogenicity and the Immunological Effects of Hypomethylating Agents in Acute Myeloid Leukemia

Study Overview
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Brief Summary
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This is a multicenter, prospective, translational study, to evaluate the immunogenic profile of AML cases according to immune checkpoint molecule expression.

Detailed Description
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This is a multicenter, prospective, translational study. Pharmacological treatments will not be object of the present study. Patients will follow the prescribed therapeutic indications according to regular clinical practice. Biological samples and clinical data will be collected at fixed timepoints. Aim of the study is to evaluate the immunogenic profile of AML cases according to immune checkpoint molecule expression. A total of 75 AML patients affected by primary or secondary AML, at diagnosis ( 45 patients) or relapse (30 patients) will be enrolled in the protocol (18 months for patient enrolment). Blood,BM and saliva samples will be collected from each patients; for patients enrolled at diagnosis, samples will be collected before and after treatment with hypomethylating agents.

Official Title
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Exploring Disease Immunogenicity and the Immunological Effects of Hypomethylating Agents in Acute Myeloid Leukemia

Conditions
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Acute Myeloid Leukemia

Intervention / Treatment
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* Genetic: Immunogenic profile


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with new diagnosis of primary or secondary AML candidate to first line treatment with hypomethylating agents (specific for Cohort 1) Patients with primary or secondary AML who relapse after/during first line treatment with hypomethylating agents (specific for Cohort 2) for each cohort: Participant is willing and able to give informed consent for participation in the study Male or Female, aged >18 years Availability of clinical data Exclusion Criteria: Age < 18 years AML M3 subtype according to FAB classification

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| At diagnosis<br>Immunogenic profile in patients affected by primary or secondary AML at diagnosis | Genetic: Immunogenic profile<br>* RNA sequencing (RNAseq), Whole exome sequencing (WES), NeoAntigens (NeoAg), Immune checkpoints analysis, Gene expression profiling<br>|
| At relapse<br>Immunogenic profile in patients affected by primary or secondary AML at relapse | Genetic: Immunogenic profile<br>* RNA sequencing (RNAseq), Whole exome sequencing (WES), NeoAntigens (NeoAg), Immune checkpoints analysis, Gene expression profiling<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of the Immunogenic profile of primary or secondary AML patients in according to the variations in expression of molecules involved in immune checkpoint | The immunogenic profile of AML cases obtained by NeoAgprediction will be related with established biological and clinical parameters (including karyotype, percentage of blasts, clinical outcome) performing RNA sequencing (RNAseq) and whole exome sequencing (WES) analysis | up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Investigation of the relationship between leukemia immunogenicity and immune checkpoint activation | the relationship between leukemia immunogenicity and immune checkpoint activation through transcriptome analysis of downstream pathways by flow cytometric analysis | up to 30 months | 
| Investigation of the activation of immune checkpoint molecules | Investigation of the activation of immune checkpoint molecules under the selective pressure of hypomethylating agents treatment by gene expression profilling | up to 30 months | 
| The investigation of the association of the immune checkpoint status with clinical outcomes | Investigation of the association of the immune checkpoint status with clinical outcomes (OS, PFS) estimated according to Kaplan-Meier. | up to 30 months | 
| The investigation of the association of the immunogenic profile with clinical outcomes | Investigation of the association of the immunogenic profile with clinical outcomes (OS, PFS) estimated according to Kaplan-Meier. | up to 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, Acute Myeloid Leukemia, Immunogenic profile, transcriptome analysis