Clinical Trial 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.
All patients diagnosed with AML (new diagnosis or relapsed/refractory 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 information/Adverse 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 relapsing/refractory patients will be included in 2
years. Of these 250 samples form relapsing/refractory 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.
