Clinical trial NCT05499611: Impact of Optical Genome Mapping in Acute Myeloblastic Leukemia
Official title: Contribution of Optical Genome Mapping to the Prognostic Classification of Acute Myeloblastic Leukemia Evaluation of the Clinical Utility of DNA Optical Mapping in the Management of Acute Myeloblastic Leukemia (COALA)
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Acute Myeloblastic Leukemia
Keywords: Optical Genome Mapping (OGM)
Acute Myeloblastic Leukemia (AML)
Complex Karyotype
Prognosis
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2022-08-12
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients with diagnosis of AML (with a minimum follow-up of 24 months)

Brief summary: A retrospective study using a new technology will be performed: the Optical Genome Mapping (OGM) on acute myelogenous leukemia (AML) samples stored at the CRB-Cancer of the Bordeaux University Hospital and annotated in the DATAML clinical database. The main objective is to estimate the proportion of AML patients for whom OGM detects at least one additional abnormality compared to conventional techniques. This study will constitute an important step in the validation of COA as a reference technique for cytogenetic analysis in AML, replacing the classical techniques, and could also constitute a first argument for redesigning the prognostic classification of AML.

Detailed description: In AML prognostic classifications, such as the ELN 2017 classification, which are used to guide treatment choices in the majority of protocols, rely heavily on genetic abnormalities. The Optical Genome Mapping (OGM) is a new technology that combines in one and the same technique the results of karyotype, FISH and SNP-Array, the latter being very little used in current practice in AML. OGM with greater sensitivity and a better resolution than the usual techniques should therefore allow us to identify more abnormalities than conventional cytogenetics; we would then like to determine whether these additional abnormalities have a prognostic impact, i.e., whether they lead to reclassification of patients initially classified as "favorable" or "intermediate" into the "unfavorable" prognostic category, with therapeutic consequences.

A retrospective study using the OGM is will be performed on samples stored at the CRB-Cancer of the Bordeaux University Hospital and annotated in the DATAML clinical database. In an original way, the focus will be on AML patients in whom 1 to 3 chromosomal abnormalities (non-recurrent WHO, not related to an unfavourable prognosis) have already been demonstrated by classical techniques, making the hypothesis that it is in this population that we would more easily have patients who could fall into the definition of the complex karyotype and thus into the unfavourable risk category.

OGM should therefore reveal a greater number of abnormalities which would allow a better definition of karyotypes with abnormalities, the number of complex and/or monosomal karyotypes and a better stratification of the prognosis of these patients with AML. This is an applied translational research study based on innovative technology that will define the place of OGM over current techniques used in the initial management of AML patients, and it may well become the new standard for cytogenetic analysis of AML in the coming years.

Eligibility criteria: Inclusion Criteria:

* Patients ≥ 18 years and ≤ 65 years of age who have been treated with intensive chemotherapy
* Diagnosis of AML (with a minimum follow-up of 24 months)
* Presence of samples included in CRB-K in the AML collection
* Cytogenetic data available: karyotype with 1-3 abnormalities present in one or more clones, excluding recurrent WHO abnormalities (t(8;21), inv(16) or t(16;16), t(9;11), t(v;11)(v;q23. 3), t(6;9), inv(3) or t(3;3) and t(9;22)) or assigned by itself to an unfavorable prognosis: -5 or del(5q); -7; -17/abn(17p).
* Molecular data available for the following genes: ASXL1, CEBPA, FLT3-ITD, NPM1, RUNX1 and TP53 (the list of genes of interest may be adapted according to the upcoming ELN 2022 classification)

Exclusion Criteria:

* Samples not included in the CRB-K (lack of consent, insufficient material...)
* Karyotype with one of the following abnormalities: (t(8;21), inv(16) or t(16;16), t(9;11), t(v;11)(v;q23.3), t(6;9), inv(3) or t(3;3), and t(9;22)) or associated with an unfavorable prognosis on its own: -5 or del(5q); -7; -17/abn(17p)
* Karyotype without clonal abnormality

Primary outcomes:
measure: Proportion of patients with more abnormalities detected by OGM than by conventional cytogenetics
timeFrame: At baseline
Secondary outcomes:
measure: Average number of additional abnormalities detected by OGM compared to conventional techniques
timeFrame: At baseline
measure: Proportion of patients reclassified as complex and/or monosomal karyotype according to current ELN definitions
timeFrame: At baseline
measure: Proportion of patients for whom a change in therapeutic management could have been proposed
timeFrame: From baseline to Month 36
measure: Comparison of overall survival and event-free survival curves of patients reclassified to the unfavorable group to those of the intermediate and unfavorable groups in a historical cohort
timeFrame: From baseline to Month 36
measure: Interobserver reproducibility for interpretation of OGM results (Fleiss Kappa coefficient)
timeFrame: At baseline
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU de Bordeaux, service Hématologie Biologique
Study officials:
References: