Ignite Creation Date:
2024-05-06 @ 10:39 AM
Last Modification Date:
2024-10-26 @ 12:33 PM
Study NCT ID:
NCT03311815
Status:
COMPLETED
Last Update Posted:
2021-02-16
First Post:
2017-10-04
Brief Title:
Diagnostic Platform to Perform Centralized and Standardized Rapid Molecular Diagnosis by Next Generation Sequencing NGS in Patients Diagnosed With Acute Myeloid Leukemia
Sponsor:
PETHEMA Foundation
Organization:
PETHEMA Foundation
Study Overview
Official Title:
A COMPREHENSIVE AND RAPID DIAGNOSIS PLATFORM OF PERSONALIZED MEDICINE FOR THE TREATMENT OF ACUTE MYELOID LEUKEMIA PROSPECTIVE MULTICENTER AND NON-INTERVENTIONAL STUDY
Status:
COMPLETED
Status Verified Date:
2021-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
NGS studies will be done in stem cell leukemic population The analysis of the samples to the diagnosis will be carried out using the 26 consensus genes ASXL1 had CBL CEBPA DNMT3A EZH2 FLT3 GATA2 IDH1 IDH2 JAK2 KIT KRAS MPL MLL NPM1 NRAS PTPN11 RUNX1 SETBP1 SF3B1 SRSF2 TET2 TP53 U2AF1 WT1 Regarding the 26 genes panel it would have the advantage that the quantification of DNA from each sample will be carried out by fluorimetry using the AmpliSeq or TruSeq on Ion platforms torrent Proton or MySeq are handled in different laboratories
Using NGS techniques the investigator will detect the recurrently mutated genes in AML to establish the biological role of each mutation
The molecular characterization of the 700 samples which are estimated to pick up during the project will consist of massive sequencing of genes recurrently mutated in AML ASXL1 had CBL CEBPA DNMT3A EZH2 FLT3 GATA2 IDH1 IDH2 JAK2 KIT KRAS MPL MLL NPM1 NRAS PTPN11 RUNX1 SETBP1 SF3B1 SRSF2 TET2 TP53 U2AF1 WT1 Found mutations will be collated in the different databases of somatic variations to establish which of them could be classified as a driver or passenger
Using NGS techniques the investigator will detect the recurrently mutated genes in AML to establish the biological role of each mutation
The molecular characterization of the 700 samples which are estimated to pick up during the project will consist of massive sequencing of genes recurrently mutated in AML ASXL1 had CBL CEBPA DNMT3A EZH2 FLT3 GATA2 IDH1 IDH2 JAK2 KIT KRAS MPL MLL NPM1 NRAS PTPN11 RUNX1 SETBP1 SF3B1 SRSF2 TET2 TP53 U2AF1 WT1 Found mutations will be collated in the different databases of somatic variations to establish which of them could be classified as a driver or passenger
Detailed Description:
All patients diagnosed with AML new diagnosis or relapsedrefractory disease can be included
This project aims to establish a platform for comprehensive diagnostic and research platform in the context of the Spanish PETHEMA cooperative group constituted by 80 institutions and seven central laboratories with extensive technological capacity
This will be a prospective multicenter non-interventional study It will be performed in 7 central laboratories Hospital Universitario la Fe Hospital Universitario de Salamanca Hospital 12 de Octubre Hospital Universitario Virgen del Rocío Hospital Reina Sofía Hospital Dr Negrín and Clínica Universidad de Navarra from the spanish PETHEMA group that will receive and process bone marrow and peripheral blood samples from AML patients at diagnosis and at resistance or first and subsequent relapses In parallel all patients will be enrolled in the ongoing PETHEMA epidemiologic registry of AML with a large number of clinical data however no safety informationAdverse Events about drug treatments will be collected Currently the PETHEMA group is reporting 600 newly diagnosed patients per year and accounts for 5000 cases in the data-base
It is expected that the investigator will analyze 450 samples from 450 newly diagnosed patients that will participate in this study in a period of 2 years 225 per year This means that roughly 40 of all AML patients from the PETHEMA group institutions will be included in the study
In addition other 250 samples from relapsingrefractory patients will be included in 2 years Of these 250 samples form relapsingrefractory patients it is expected that 150 samples will be drawn from patients in whom the sample was already analyzed at diagnosis in the current study and 100 samples will be drawn form 100 additional patients that were not previously included in the study at the initial diagnosis So the expected distribution of analyzed samples will be 450 at diagnosis 150 resampling at first relapse from patients already analyzed at diagnosis and 100 samples at first or subsequent relapse from patients not included in the study at the time of diagnosis The investigator expect at least 500 patients and 700 samples
Molecular diagnosis by NGS will be rapidly reported to the treating physician 48-72 hours in order to facilitate inclusion of patients in potential targeted therapy trials in AML
Through the analysis of leukemic cells in samples from a large cohort of patients treated homogeneously it is intended to delve into the prognostic value of genetic lesions that are observed at diagnosis by means of a large panel of mutations by next-generation sequencing Thanks to this ambitious cooperative study the investigator will be in an unprecedented and novel situation to understand the cellular mechanisms associated with chemoresistance of leukemic cells This could allow us to design new therapeutic strategies of personalized medicine that will be able to eradicate these cells with minimal toxic effects on patients with AML
This project aims to establish a platform for comprehensive diagnostic and research platform in the context of the Spanish PETHEMA cooperative group constituted by 80 institutions and seven central laboratories with extensive technological capacity
This will be a prospective multicenter non-interventional study It will be performed in 7 central laboratories Hospital Universitario la Fe Hospital Universitario de Salamanca Hospital 12 de Octubre Hospital Universitario Virgen del Rocío Hospital Reina Sofía Hospital Dr Negrín and Clínica Universidad de Navarra from the spanish PETHEMA group that will receive and process bone marrow and peripheral blood samples from AML patients at diagnosis and at resistance or first and subsequent relapses In parallel all patients will be enrolled in the ongoing PETHEMA epidemiologic registry of AML with a large number of clinical data however no safety informationAdverse Events about drug treatments will be collected Currently the PETHEMA group is reporting 600 newly diagnosed patients per year and accounts for 5000 cases in the data-base
It is expected that the investigator will analyze 450 samples from 450 newly diagnosed patients that will participate in this study in a period of 2 years 225 per year This means that roughly 40 of all AML patients from the PETHEMA group institutions will be included in the study
In addition other 250 samples from relapsingrefractory patients will be included in 2 years Of these 250 samples form relapsingrefractory patients it is expected that 150 samples will be drawn from patients in whom the sample was already analyzed at diagnosis in the current study and 100 samples will be drawn form 100 additional patients that were not previously included in the study at the initial diagnosis So the expected distribution of analyzed samples will be 450 at diagnosis 150 resampling at first relapse from patients already analyzed at diagnosis and 100 samples at first or subsequent relapse from patients not included in the study at the time of diagnosis The investigator expect at least 500 patients and 700 samples
Molecular diagnosis by NGS will be rapidly reported to the treating physician 48-72 hours in order to facilitate inclusion of patients in potential targeted therapy trials in AML
Through the analysis of leukemic cells in samples from a large cohort of patients treated homogeneously it is intended to delve into the prognostic value of genetic lesions that are observed at diagnosis by means of a large panel of mutations by next-generation sequencing Thanks to this ambitious cooperative study the investigator will be in an unprecedented and novel situation to understand the cellular mechanisms associated with chemoresistance of leukemic cells This could allow us to design new therapeutic strategies of personalized medicine that will be able to eradicate these cells with minimal toxic effects on patients with AML
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None