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

• Conditions: Acute Myeloid Leukemia

• Registration Number: NCT03789981
• Lead Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Brief Summary

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

Detailed Description

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 Timeline

• Study First Submitted: 2018-11-08
• Study First Submitted QC: 2018-12-21
• Study First Posted: 2018-12-31
• Study Start: 2019-07-19
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-25
• Last Update Posted: 2021-02-26
• Primary Completion: 2021-12
• Study Completion: 2021-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 75

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Evaluation of the Immunogenic profile of primary or secondary AML patients in according to the variations in expression of molecules involved in immune checkpoint	up to 30 months	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

Secondary Outcome Measures

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

Trial Locations

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

IRCCS AOU S. Martino Genova; 🇮🇹 Genova, GE, Italy

Ospedale G. Da Saliceto; 🇮🇹 Piacenza, PC, Italy

Irccs Crob; 🇮🇹 Rionero in Vulture, PZ, Italy

Osp. S. Maria delle Croci; 🇮🇹 Ravenna, RA, Italy

Ospedale degli Infermi; 🇮🇹 Rimini, RN, Italy

AOU Senese; 🇮🇹 Siena, SI, Italy

Università di Torino; 🇮🇹 Orbassano, TO, Italy

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