Kinetics and Impact on Survival of MRD in AML Patients Receiving Azacitidine and Venetoclax

A Multicentric, Prospective Study Addressing the Kinetics and Impact on Survival of Measurable Residual Disease in Acute Myeloid Leukemia Patients Receiving Azacitidine and Venetoclax

The goal of this no-profit, multicenter, biological, non-pharmacologic study is to evaluate minimal residual disease (MRD) in patients treated with Azacitidine and Venetoclax according to clinical practice.

The main questions it aims to answer are:

1. kinetics of disease response on treatment with Azacitidine and Venetoclax through the evaluation of MRD with both cytofluorimetric and molecular techniques
2. impact of MRD on survival outcomes. To this end, bone marrow samples will be collected at pre-defined time-points during treatment and MRD will be assessed.

Study Overview

• Status: Not yet recruiting
• Conditions: Minimal Residual Disease; AML, Adult
• Intervention / Treatment: Diagnostic test: MRD assessment

Detailed Description

This is a multicentric biological study at evaluating MRD kinetics during treatment with Azacitidine and Venetoclax as well as the impact of MRD on survival outcomes.

Newly diagnosed, previously untreated, patients with AML, including de novo, secondary and therapy-related, receiving front-line therapy with Azacitidine and Venetoclax according to clinical practice will be included.

Response assessment will be performed on BM aspirate according to ELN2022 response criteria. MRD evaluation will be performed on BM at pre-defined time-points during treatment. MRD assessment will be performed centrally in order to harmonize response evaluation.

• Study Type: Interventional
• Enrollment (Estimated): 225
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Paola Fazi; Phone Number: 0670390528; Email: p.fazi@gimema.it
• Study Contact Backup: Name: Enrico Crea; Phone Number: 0670390514; Email: e.crea@gimema.it

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Subject must be ≥ 18 years of age
• Subject has diagnosis of AML according to WHO 2016
• Subject has newly diagnosed, previously untreated, AML, including de novo, secondary and therapy-related (cytoreduction with hydroxyurea is admitted prior treatment start)
• Subject is planned to receive front-line therapy with Azacitidine and Venetoclax
• Subject is ineligible for intensive induction chemotherapy according to investigator assessment according to clinical practice
• Subject must have assessable MRD by flow cytometry at screening BM evaluation
• Signed written informed consent according to ICH/EU/GCP and national local laws

Exclusion Criteria:

• Diagnosis of BCR::ABL1-positive AML
• Diagnosis of APL
• AML with CNS involvement.
• AML with extra-medullary localizations
• Patients' unwillingness or inability to comply with the protocol requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: MRD evaluation; Evaluation of MRD at pre-defined timepoints in AML patients treated with Azacitidine and Venetoclax	Diagnostic test: MRD assessment; Bone marrow withdrawal for MRD quantification

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of MRD-negative patients within cycle 4	Number of patients without minimal residual disease within cycle 4 on the total of subjects receiving at least one dose of study medication	4 months

Collaborators and Investigators

• Sponsor: Gruppo Italiano Malattie EMatologiche dell'Adulto
• Investigators: Principal Investigator: Antonio Curti, Division of Hematology IRCCS Azienda Ospedaliero-Universitaria di Bologna

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: October 13, 2023
• First Submitted That Met QC Criteria: October 13, 2023
• First Posted (Actual): October 19, 2023

Study Record Updates

• Last Update Posted (Actual): April 10, 2024
• Last Update Submitted That Met QC Criteria: April 9, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: AML; Venetoclax; Azacitidine; Minimal rsidual disease
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Neoplastic Processes; Neoplasm, Residual
• Other Study ID Numbers: AML2723

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No