Italian Non-Interventional Study of FLT3 Mutated AML Patients

AML Clinical Trial

— FLAM  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03547258
• Other study ID #: IRST204.01
• Status: Recruiting
• Start date: July 18, 2018
• Est. completion date: May 2021

Study information

• Verified date: April 2020
• 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 an observational study involving a retrospective and prospective collection of clinical and molecular data regarding patients with AML with FLT3+ mutations

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 800
• Est. completion date: May 2021
• Est. primary completion date: May 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• AML
• FLT3-ITD Mutation
• FLT3-TKD Mutation

Intervention

Genetic:
• Clinical and Molecular data collection
Clinical and Molecular data collection at diagnosis, during treatment and at each relapse

Locations

Country	Name	City	State
Italy	AOU Ospedali riuniti di Ancona	Ancona	AN
Italy	AOU Policlinico Bari - Ematologia	Bari	BA
Italy	Università di Bologna - DIMES	Bologna	BO
Italy	ASST Spedali di Brescia	Brescia	BS
Italy	Azienda Ospedaliera G. Brotzu	Cagliari	CA
Italy	Ematologia - Azienda Ospedaliera "Pugliese Ciaccio" di Catanzaro	Catanzaro	CZ
Italy	AOU Universitaria Arcispedale Sant'Anna	Cona	Ferrara
Italy	Azienda Ospedaliera S. Croce e Carle	Cuneo	CN
Italy	AOU Careggi	Firenze	FI
Italy	Ospedale Vito Fazzi di Lecce	Lecce	LE
Italy	Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST)	Meldola	FC
Italy	AOU Policlinico Gaetano Martino	Messina	ME
Italy	Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico	Milano	MI
Italy	Istituto Europeo di Oncologia	Milano	MI
Italy	Ospedale San Raffaele	Milano	MI
Italy	AO Universitaria Federico II	Napoli
Italy	AOU Maggiore della carità	Novara
Italy	Università di Torino - Ospedale San Luigi Gonzaga	Orbassano	TO
Italy	Ospedali Riuniti Villa Sofia-Cervello	Palermo	PA
Italy	Azienda Ospedaliero-Universitaria di Parma - Ematologia e CTMO	Parma	PR
Italy	AOU Santa Maria della Misericordia - Ematologia	Perugia
Italy	Ospedale "Guglielmo da Saliceto"	Piacenza	PC
Italy	UO Ematologia, Ospedale S.Maria delle Croci	Ravenna	RA
Italy	Grande Ospedale Metropolitano	Reggio Calabria	RC
Italy	Ospedale infermi di Rimini	Rimini	RN
Italy	Irccs Crob	Rionero In Vulture	Potenza
Italy	Fondazione Policlinico Universitario Agostino Gemelli	Roma
Italy	AOU San Giovannidi Dio e Ruggi - ematologia	Salerno	SA
Italy	IRCCS Casa sollievo della sofferenza	San Giovanni Rotondo	FG
Italy	AOC di Ematologia - AOU Senese	Siena	SI
Italy	A.O. Ordine Mauriziano Torino	Torino	TO
Italy	AOU Città della Salute e della Scienza di Torino	Torino	TO
Italy	Divisione di Ematologia - Università di Udine	Udine	UD

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	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	transplantation percentage	percentage of FLT3 mutated AML patients undergoing transplantation	up to 24 months
Secondary	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
Secondary	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