Italian Non-Interventional Study of FLT3 Mutated AML Patients (FLAM)

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

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

Study Overview

• Status: Unknown
• Conditions: AML; FLT3-ITD Mutation; FLT3-TKD Mutation
• Intervention / Treatment: Genetic: Clinical and Molecular data collection

Detailed Description

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:

1. Retrospective phase: clinical and molecular data of AML patients with FLT3+ mutations detected at diagnosis or at any refractory/relapse state will be collected.
2. 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.

• Study Type: Observational
• Enrollment (Anticipated): 800

Contacts and Locations

• Study Contact: Name: Oriana Nanni; Phone Number: +390543739266; Email: oriana.nanni@irst.emr.it

Study Locations

• Italy
  • Napoli, Italy, 80131
    • Recruiting
    • AO Universitaria Federico II
  • Novara, Italy, 28100
    • Recruiting
    • AOU Maggiore della Carità
    • Contact: Monia Lunghi, MD, PhD
  • Perugia, Italy, 06129
    • Recruiting
    • AOU Santa Maria della Misericordia - Ematologia
    • Contact: Maria Paola Martelli, Prof.ssa
  • Roma, Italy, 00168
    • Recruiting
    • Fondazione Policlinico Universitario Agostino Gemelli
    • Contact: Simona Sica, Prof
  • AN
    • Ancona, AN, Italy, 60126
      • Recruiting
      • AOU Ospedali Riuniti di Ancona
  • BA
    • Bari, BA, Italy, 70124
      • Recruiting
      • AOU Policlinico Bari - Ematologia
  • BO
    • Bologna, BO, Italy, 40138
      • Recruiting
      • Università di Bologna - DIMES
      • Contact: Cristina Papayannidis
  • BS
    • Brescia, BS, Italy, 25123
      • Recruiting
      • ASST Spedali di Brescia
  • CA
    • Cagliari, CA, Italy, 09121
      • Recruiting
      • Azienda Ospedaliera G. Brotzu
  • CN
    • Cuneo, CN, Italy, 12100
      • Recruiting
      • Azienda Ospedaliera S. Croce e Carle
      • Contact: Daniele Mattei
  • CZ
    • Catanzaro, CZ, Italy, 88100
      • Recruiting
      • Ematologia - Azienda Ospedaliera "Pugliese Ciaccio" di Catanzaro
      • Contact: Stefano Molica
  • FC
    • Meldola, FC, Italy, 47014
      • Recruiting
      • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)
      • Contact: Giovanni Martinelli, MD; Phone Number: 0390543739100; Email: giovanni.martinelli@irst.emr.it
      • Sub-Investigator: Maria Benedetta Giannini, MD
  • FG
    • San Giovanni Rotondo, FG, Italy, 71013
      • Recruiting
      • IRCCS Casa Sollievo della Sofferenza
      • Contact: Nicola Cascavilla, DR
  • FI
    • Firenze, FI, Italy, 50134
      • Recruiting
      • AOU Careggi
      • Contact: Alberto Bosi
  • Ferrara
    • Cona, Ferrara, Italy, 44124
      • Recruiting
      • AOU Universitaria Arcispedale Sant'Anna
      • Contact: Gian Matteo Rigolin, Prof
  • LE
    • Lecce, LE, Italy, 73100
      • Recruiting
      • Ospedale Vito Fazzi di Lecce
      • Contact: Nicola Di Renzo, DR
  • ME
    • Messina, ME, Italy, 98125
      • Recruiting
      • AOU Policlinico Gaetano Martino
      • Contact: Caterina Musolino
  • MI
    • Milano, MI, Italy, 20132
      • Recruiting
      • Ospedale San Raffaele
      • Contact: Fabio Ciceri
    • Milano, MI, Italy, 20122
      • Recruiting
      • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
      • Contact: Nicola Stefano Fracchiolla, MD
    • Milano, MI, Italy, 20141
      • Recruiting
      • Istituto Europeo di Oncologia
      • Contact: Elisabetta Todisco
  • PA
    • Palermo, PA, Italy, 90146
      • Recruiting
      • Ospedali Riuniti Villa Sofia-Cervello
      • Contact: Francesco Fabbiano
  • PC
    • Piacenza, PC, Italy, 29121
      • Recruiting
      • Ospedale "Guglielmo da Saliceto"
  • PR
    • Parma, PR, Italy, 43125
      • Recruiting
      • Azienda Ospedaliero-Universitaria di Parma - Ematologia e CTMO
      • Contact: Giovanni Roti
  • Potenza
    • Rionero In Vulture, Potenza, Italy, 85028
      • Recruiting
      • Irccs Crob
      • Contact: Pellegrino Mustu
  • RA
    • Ravenna, RA, Italy, 48121
      • Recruiting
      • UO Ematologia, Ospedale S.Maria delle Croci
  • RC
    • Reggio Calabria, RC, Italy, 89123
      • Recruiting
      • Grande Ospedale Metropolitano
      • Contact: Esther Oliva
  • RN
    • Rimini, RN, Italy, 47923
      • Recruiting
      • Ospedale Infermi di Rimini
      • Contact: Anna Maria Mianulli, MD
  • SA
    • Salerno, SA, Italy, 84131
      • Recruiting
      • AOU San Giovannidi Dio e Ruggi - ematologia
      • Contact: Carmine Selleri
  • SI
    • Siena, SI, Italy, 53100
      • Recruiting
      • AOC di Ematologia - AOU Senese
      • Contact: Monica Bocchia
  • TO
    • Orbassano, TO, Italy, 10043
      • Recruiting
      • Università di Torino - Ospedale San Luigi Gonzaga
    • Torino, TO, Italy, 10126
      • Recruiting
      • AOU Citta della Salute e della Scienza di Torino
    • Torino, TO, Italy, 10128
      • Recruiting
      • A.O. Ordine Mauriziano Torino
      • Contact: Alessandro Cignetti
  • UD
    • Udine, UD, Italy, 33100
      • Recruiting
      • Divisione di Ematologia - Università di Udine
      • Contact: Anna Candoni

Participation Criteria

Eligibility Criteria

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

• Sampling Method: Probability Sample

Study Population

All consecutive patient with FLT3 mutated AML documented at diagnosis or at the time of relapse/refractory state treated in the participating center. With regards to the retrospective collection, data from the eligible and acconsenting patients will be retrieved since 2012, that is, when the evaluation of FLT3 mutation was almost routine in the centers considered in the study.

Description

Inclusion criteria:

1. AML patients
2. Male or Female
3. Aged ≥ 18 years
4. FLT3 mutations (ITD or TKD) positive tests performed at diagnosis or at relapse.
5. 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
AML patients; Clinical and Molecular data collection of AML Patients with FLT3 mutations (ITD or TKD)	Genetic: Clinical and Molecular data collection; Clinical and Molecular data collection at diagnosis, during treatment and at each relapse

What is the study measuring?

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

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2018
• Primary Completion (Anticipated): May 1, 2021
• Study Completion (Anticipated): May 1, 2021

Study Registration Dates

• First Submitted: May 11, 2018
• First Submitted That Met QC Criteria: May 23, 2018
• First Posted (Actual): June 6, 2018

Study Record Updates

• Last Update Posted (Actual): April 21, 2020
• Last Update Submitted That Met QC Criteria: April 20, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: AML; Italian observational study; FLT3-ITD Mutation; FLT3-TKD Mutation
• Other Study ID Numbers: IRST204.01

Drug and device information, study documents

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