Molecular Diagnostic Platform for AML

Acute Myeloid Leukemia (AML) Clinical Trial

Official title:

Developing a Molecular Diagnostic Platform for Personalized Medicine for Acute Myeloid Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04446741
• Other study ID #: PCR-LMA
• Status: Recruiting
• Start date: October 1, 2019
• Est. completion date: October 2022

Study information

• Verified date: September 2021
• Source: PETHEMA Foundation
• Contact: Olga Garcia
• Phone: +34 609 128 678
• Email: publi[@]fundacionpethema.es
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This will be a translational study without any therapeutic intervention, for the purpose of analyzing the diagnostic and molecular results / characterization of adult patients with AML, regardless of the treatment they receive. Newly diagnosed or relapsed/resistant AML patients will be included.

Description:

This will be a multicenter, translational study without any therapeutic intervention. It will be conducted at 7 central laboratories (Hospital Universitari i Politècnic La Fe, Hospital Universitario de Salamanca, Hospital 12 de Octubre, Hospital Universitario Virgen del Rocío, Hospital Dr. Negrín de Las Palmas de Gran Canaria, Hospital Reina Sofía de Córdoba and Clínica Universidad de Navarra) belonging to the Spanish PETHEMA Group. The laboratories will receive and process bone marrow and peripheral blood samples of patients with AML at the time of the initial diagnosis or at relapse or resistance (first or subsequent relapse/resistance). The demographic data and clinical characteristics of the patients and of the AML, morphological and molecular response will be collected in case report forms (CRFs). Since the aim of this study is the molecular diagnosis of AML, all patients with AML will be included, regardless of the treatment (or no treatment at all) they receive.

The physicians will receive the report about the molecular diagnosis for FLT3, NPM1, CBF and PML/RARa quickly (<48-96 hours), in order to provide them with knowledge of the mutational status, that may cause changes to be made during the initial management of the disease.

The aim of this project is to set up this rapid screening and diagnostic platform for AML by having specimens sent to 7 centralized reference laboratories across the country, where the molecular characteristics of leukemic cells will be analyzed by qRT-PCR and NGS technologies with high quality standards. This platform will provide homogeneous criteria for assessing the biological characteristics of the different entities that make up the disease.

It is expected that samples of marrow and/or blood of 700 patients with AML will be analyzed per year.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 2000
• Est. completion date: October 2022
• Est. primary completion date: October 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 99 Years

Eligibility

Inclusion Criteria:

• Have voluntarily given informed consent for the sending and processing of biological specimens, as well as for the analysis and reporting of the results on the mutation status of their AML.

• Age greater than or equal to 18 years.

• Morphological diagnosis of AML or acute leukemia of ambiguous lineage according to WHO criteria at diagnosis, relapse or resistance.

Exclusion Criteria:

• Inability of the patient or his/her legal representative to understand and voluntarily sign the informed consent form

Related Conditions & MeSH terms

• Acute Myeloid Leukemia (AML)
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Locations

Country	Name	City	State
Spain	Hospital Universitario Reina Sofía	Córdoba
Spain	Hospital Universitario de Gran Canaria Dr. Negrín	Las Palmas De Gran Canaria
Spain	Hospital Doce de Octubre	Madrid
Spain	Clínica Universidad de Navarra	Pamplona
Spain	Hospital Universitario de Salamanca	Salamanca
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Universitario La Fe	Valencia

Sponsors (1)

Lead Sponsor	Collaborator
PETHEMA Foundation

Country where clinical trial is conducted

Spain, 

References & Publications (5)

Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Löwenberg B, Bloomfield CD. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017 Jan 26;129(4):424-447. doi: 10.1182/blood-2016-08-733196. Epub 2016 Nov 28. Review. — View Citation

Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, Dombret H, Fenaux P, Grimwade D, Larson RA, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz MA, Sierra J, Tallman MS, Löwenberg B, Bloomfield CD; European LeukemiaNet. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood. 2010 Jan 21;115(3):453-74. doi: 10.1182/blood-2009-07-235358. Epub 2009 Oct 30. Review. — View Citation

Juliusson G, Antunovic P, Derolf A, Lehmann S, Möllgård L, Stockelberg D, Tidefelt U, Wahlin A, Höglund M. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood. 2009 Apr 30;113(18):4179-87. doi: 10.1182/blood-2008-07-172007. Epub 2008 Nov 13. — View Citation

Ley TJ, Mardis ER, Ding L, Fulton B, McLellan MD, Chen K, Dooling D, Dunford-Shore BH, McGrath S, Hickenbotham M, Cook L, Abbott R, Larson DE, Koboldt DC, Pohl C, Smith S, Hawkins A, Abbott S, Locke D, Hillier LW, Miner T, Fulton L, Magrini V, Wylie T, Glasscock J, Conyers J, Sander N, Shi X, Osborne JR, Minx P, Gordon D, Chinwalla A, Zhao Y, Ries RE, Payton JE, Westervelt P, Tomasson MH, Watson M, Baty J, Ivanovich J, Heath S, Shannon WD, Nagarajan R, Walter MJ, Link DC, Graubert TA, DiPersio JF, Wilson RK. DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome. Nature. 2008 Nov 6;456(7218):66-72. doi: 10.1038/nature07485. — View Citation

Miller CA, Wilson RK, Ley TJ. Genomic landscapes and clonality of de novo AML. N Engl J Med. 2013 Oct 10;369(15):1473. doi: 10.1056/NEJMc1308782. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of FLT3, NPM1 and CEBPa mutations	Frequency of each of the standard screening panel molecular alterations studied in the AML patients (FLT3, NPM1 and CEBPa), both in newly diagnosed and relapsed/resistant disease.	Baseline
Secondary	Frequency of mutations detected by Next Generation Sequency (NGS)	Frequency of mutations detected by NGS PCR (23 genes: FLT3, NPM1, DNMT3A, IDH2, IDH1, TET2, RUNX1, TP53, NRAS, WT1, PTPN11, KIT, U2AF1, KRAS, SMC1A, SMC3, PHF6, STAG2, RAD21, FAM5C, EZH2 and HNRNPK; if new genes are described,the panel can be extended) in every sample (diagnosis, relapse)	Baseline
Secondary	Frequency of mutations detected by conventional PCR (FLT3, NPM1 and CEBPa) in every sample (diagnosis, relapse)	Frequency of each of the standard screening panel molecular alterations studied by the conventional PCR in the AML patients (FLT3, NPM1 and CEBPa), both in newly diagnosed and relapsed/resistant disease.	Baseline