Exploring Disease Immunogenicity and the Immunological Effects of Hypomethylating Agents in Acute Myeloid Leukemia (Immune-AML)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Acute Myeloid Leukemia
• Intervention / Treatment: Genetic: Immunogenic profile

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 Type: Observational
• Enrollment (Estimated): 75

Contacts and Locations

Study Locations

• Italy
  • Novara, Italy, 28100
    • AOU Maggiore della Carita
  • Udine, Italy, 33010
    • AOU di Udine
  • BS
    • Brescia, BS, Italy, 25123
      • AO Spedali Civili di Brescia
  • FC
    • Meldola, FC, Italy, 47014
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy, 71013
      • IRCCS Casa sollievo sofferenza
  • GE
    • Genova, GE, Italy, 16132
      • IRCCS AOU S. Martino Genova
  • PC
    • Piacenza, PC, Italy, 29121
      • Ospedale G. Da Saliceto
  • PZ
    • Rionero in Vulture, PZ, Italy, 85028
      • Irccs Crob
  • RA
    • Ravenna, RA, Italy, 48121
      • Osp. S. Maria delle Croci
  • RN
    • Rimini, RN, Italy, 47923
      • Ospedale Degli Infermi
  • SI
    • Siena, SI, Italy, 53100
      • AOU Senese
  • TO
    • Orbassano, TO, Italy, 10043
      • Università di Torino
    • Torino, TO, Italy, 10128
      • AO Ordine Mauriziano di Torino
  • TV
    • Treviso, TV, Italy, 31100
      • Azienda ULSS2 Marca Trevigiana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

AML patients affected by primary or secondary AML, at diagnosis or relapse

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
At diagnosis; Immunogenic profile in patients affected by primary or secondary AML at diagnosis	Genetic: Immunogenic profile; RNA sequencing (RNAseq), Whole exome sequencing (WES), NeoAntigens (NeoAg), Immune checkpoints analysis, Gene expression profiling
At relapse; Immunogenic profile in patients affected by primary or secondary AML at relapse	Genetic: Immunogenic profile; RNA sequencing (RNAseq), Whole exome sequencing (WES), NeoAntigens (NeoAg), Immune checkpoints analysis, Gene expression profiling

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Investigators: Study Chair: Giovanni Martinelli, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)

Study record dates

Study Major Dates

• Study Start (Actual): July 19, 2019
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: November 8, 2018
• First Submitted That Met QC Criteria: December 21, 2018
• First Posted (Actual): December 31, 2018

Study Record Updates

• Last Update Posted (Actual): September 20, 2024
• Last Update Submitted That Met QC Criteria: September 18, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; AML; transcriptome analysis; Immunogenic profile
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: IRSTB082

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No