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

Acute Myeloid Leukemia Clinical Trial

— Immune-AML  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03789981
• Other study ID #: IRSTB082
• Status: Recruiting
• Start date: July 19, 2019
• Est. completion date: December 2021

Study information

• Verified date: February 2021
• Source: Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori
• Contact: Oriana Nanni
• Phone: +390543739266
• Email: oriana.nanni[@]irst.emr.it
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75
• Est. completion date: December 2021
• Est. primary completion date: December 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myeloid Leukemia
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Genetic:
• Immunogenic profile
RNA sequencing (RNAseq), Whole exome sequencing (WES), NeoAntigens (NeoAg), Immune checkpoints analysis, Gene expression profiling

Locations

Country	Name	City	State
Italy	AO Spedali Civili di Brescia	Brescia	BS
Italy	IRCCS AOU S. Martino Genova	Genova	GE
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)	Meldola	FC
Italy	AOU Maggiore della Carità	Novara
Italy	Università di Torino	Orbassano	TO
Italy	Ospedale G. Da Saliceto	Piacenza	PC
Italy	Osp. S. Maria delle Croci	Ravenna	RA
Italy	Ospedale degli Infermi	Rimini	RN
Italy	Irccs Crob	Rionero in Vulture	PZ
Italy	IRCCS Casa sollievo sofferenza	San Giovanni Rotondo	Foggia
Italy	AOU Senese	Siena	SI
Italy	AO Ordine Mauriziano di Torino	Torino	TO
Italy	Azienda ULSS2 Marca Trevigiana	Treviso	TV
Italy	AOU di Udine	Udine

Sponsors (1)

Lead Sponsor	Collaborator
Istituto Scientifico Romagnolo per lo Studio e la cura dei Tumori

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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