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

N/AActive Not RecruitingNCT03789981

Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS75 enrolled

Overview

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

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Acute Myeloid Leukemia

Interventions

Immunogenic profileGENETIC

RNA sequencing (RNAseq), Whole exome sequencing (WES), NeoAntigens (NeoAg), Immune checkpoints analysis, Gene expression profiling

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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: 2. Participant is willing and able to give informed consent for participation in the study 3. Male or Female, aged \>18 years 4. Availability of clinical data Exclusion Criteria: 1. Age \< 18 years 2. AML M3 subtype according to FAB classification

Locations (14)

AO Spedali Civili di Brescia

Brescia, BS, Italy

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)

Meldola, FC, Italy

IRCCS Casa sollievo sofferenza

San Giovanni Rotondo, FOGGIA, Italy

Outcomes

Primary Outcomes

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

Time frame: up to 30 months

Secondary Outcomes

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

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: up to 30 months

Data from ClinicalTrials.gov

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