Italian Non-Interventional Study of FLT3 Mutated AML Patients

Study Overview
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Brief Summary
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This is an observational study involving a retrospective and prospective collection of clinical and molecular data regarding patients with AML with FLT3+ mutations

Detailed Description
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This is an observational study involving a retrospective and prospective collection of clinical and molecular data. Patients will follow their regular diagnostic and clinical practice. Thus, no additional procedure/blood withdrawal will be performed. The study will be conducted as follows: Retrospective phase: clinical and molecular data of AML patients with FLT3+ mutations detected at diagnosis or at any refractory/relapse state will be collected. Prospective phase: clinical and molecular data of each new FLT3+ AML patient identified in participating centers at diagnosis or at any refractory/relapse state will be collected prospectively. Every effort will be done to include all consecutive patients, in order to avoid selection bias. For patients with a mutation found at the time of disease relapse, any effort will be done to collect all the clinical and molecular information since the time of diagnosis. The Primary objective of this study is to analyze how FLT3 mutational status evolve during the management of the disease looking at the percentage of patients with no FLT3 mutations at diagnosis who relapse with a new FLT3 mutation detected, and the percentage of FLT3 positive AML patients that after having obtained a Complete Remission relapse with FLT3 negative. The secondary objective of the study is to investigate the association between different FLT3 mutations and the clinical, molecular and biological information.

Official Title
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Italian Non-Interventional Study of FMS-like Tyrosine Kinase (FLT3) Mutated Acute Myeloid Leukemia (AML) Patients

Conditions
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AML, FLT3-ITD Mutation, FLT3-TKD Mutation

Intervention / Treatment
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* Genetic: Clinical and Molecular data collection


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: AML patients Male or Female Aged ≥ 18 years FLT3 mutations (ITD or TKD) positive tests performed at diagnosis or at relapse. Participant is willing and able to give informed consent for participation in the study. Exclusion criteria: 1. To be currently involved in experimental clinical protocol, or have been treated with experimental drugs are not exclusion criteria.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| AML patients<br>Clinical and Molecular data collection of AML Patients with FLT3 mutations (ITD or TKD) | Genetic: Clinical and Molecular data collection<br>* Clinical and Molecular data collection at diagnosis, during treatment and at each relapse<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| percentage of patients FLT3 negative at diagnosis who relapse FLT3 positive; | description of how the FLT3 mutational status changes during the course and management of the disease | up to 24 months | 
| percentage of patients FLT3 positive at diagnosis who relapse FLT3 negative | description of how the FLT3 mutational status changes during the course and management of the disease | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| objective overall response rate (ORR) | the objective overall response rate (ORR) defined as the proportion of patients with a partial or response (CR, CRi, CRp) response, to initial treatment and in case of salvage; | up to 24 months | 
| disease-free survival (DFS) | disease-free survival (DFS) after first CR and after CR2/CR3, if applicable, defined as the time since CR (or CR2 or CR3) to disease relapse or death for any cause, whichever occurs first. | up to 24 months | 
| overall survival (OS) | overall survival (OS) defined as the time since date of diagnosis until death for any cause or the last available patient contact. | up to 24 months | 
| Percentage of AML patients with specific types of FLT3 mutations | Percentage of AML patients with specific types of FLT3 mutations, at initial diagnosis and at disease relapse | up to 24 months | 
| distribution of specific FLT3 mutations in AML patients | distribution of specific FLT3 mutations in AML patients according to: age, WBC, LDH, cytogenetics, NPM1, CEBPA alterations, IDH1/2, tp53, DNMT3A, secondary vs de novo AML; | up to 24 months | 
| frequency of the different methods used to evaluate (Minimal residual disease) MRD | the frequency of the different methods used to evaluate MRD such as, wt1 ratio or the fusion transcript level by Reverse transcription polymerase chain reaction (RT-PCR); percentage of patients performing FLT3 ITD analysis by Next Generation Sequencing (NGS); | up to 24 months | 
| FLT3-ITD allelic ratio | FLT3-ITD allelic ratio defined as the ratio of the area under the curve of mutant and wild type alleles (mutant/totalFLT3) obtained after Fragment analysis for FLT3-ITD; | up to 24 months | 
| transplantation percentage | percentage of FLT3 mutated AML patients undergoing transplantation | up to 24 months | 
| evaluation of modifications in terms of quality of life (QoL) of patients with FLT3 mutated AML | scores for each patient and each scale as well as a summary QoL score will be computed according to the EORTC QLQ-C3 (quality of life questionnaire) manual | up to 24 months | 
| retrospective collection of surrogate measures of QoL | the surrogate measures of QoL , as the number and days of hospitalizations per patient, number of clinical visits per patient, number of access in Day Hospital and Emergency Care Units per patient, and the use of antalgic drugs and neuro-active drugs, will be expressed in terms of mean values per patient or through proportions | up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AML, Italian observational study, FLT3-ITD Mutation, FLT3-TKD Mutation