Clinical trial NCT05541224: A Retrospective Epidemiologic Registry to Gain Insight Into the Characteristics and Prognosis of AML Patients According to the Routinely Used Genetic and Biologic Markers
Official title: A Retrospective Epidemiologic Registry to Gain Insight Into the Characteristics and Prognosis of AML Patients According to the Routinely Used Genetic and Biologic Markers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Acute Myeloid Leukemia
Keywords: De novo Acute Myeloid Leukemia
Relapsed/refractory Acute Myeloid Leukemia
Lead sponsor: PETHEMA Foundation
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2022-09-15
Enrollment: 6917
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients diagnosed with AML (new diagnosis or relapsed/refractory disease). These patients must meet all the inclusion criteria and none of the exclusion criteria specified.

Brief summary: This is a retrospective, translational, epidemiologic, multicenter, non-interventional study (No EPA study) to provide insights into disease epidemiology, disease biology, treatment regimens, and clinical outcomes of patients with acute myeloblastic leukemia (AML) in routine clinical practice according to their molecular markers.

The primary objective of the study is to describe the use of the main molecular markers (FLT3 and NPM1) in the real-life according of the type of AML, treating institution, patients' characteristics, and disease status.

Detailed description: This is a retrospective, translational, epidemiologic, multicenter, non-interventional study (No EPA study) to provide insights into disease epidemiology, disease biology, treatment regimens, and clinical outcomes of patients with AML in routine clinical practice according to their molecular markers.

Once it has been confirmed that all selection criteria for the study have been met and informed consent has been obtained, the subject will be considered enrolled in the study and the investigator can proceed to collect data from their medical record by completing a case report (CRF).

The study contemplates the retrospective collection of data from disease diagnosis to the start of the study. Only data obtained before the start of the study will be collected in order to ensure they are retrospective in nature.

The study will be conducted following the requirements contained in the Declaration of Helsinki (Fortaleza, Brazil 2013) and in accordance with the current Spanish legislation with regard to conducting observational studies (Ministerial Order SAS/3470/2009).

The primary objective of the study is to describe the use of the main molecular markers (FLT3 and NPM1) in the real-life according of the type of AML, treating institution, patients' characteristics, and disease status.

This project will be conducted in the Spanish PETHEMA cooperative group, constituted by 60 institutions and seven main central laboratories with extensive technological capacity. All patients will be included in the ongoing PETHEMA epidemiologic registry of AML with the purpose to collect a large number, additional and non-pre-existent clinical data, including first-line and salvage treatment schedules and outcomes of each patient.

For this study the PETHEMA AML registry will be enlarged seeking for new cases not previously reported. The data base information will be updated emphasizing for the capture of new data on molecular screening tests performed on a routine basis (FLT3, NPM1, and others). For these purpose, information will be systematically requested from the main PETHEMA laboratories. Therapies and clinical outcome data will be retrospectively collected. This is a one-step study without intervention, in which all analyses will be performed at the end of the database completion.

Eligibility criteria: Inclusion Criteria:

1. All adult patients with AML (excluding APL) according to the WHO criteria (2008), regardless of the treatment administered by their treating physician.
2. AML at diagnosis and at relapse or refractoriness.
3. Patients from institutions participating in the ongoing PETHEMA AML registry.
4. Patients with information about the molecular screening including FLT3 with or without NPM1 mutations (including positive/negative or not performed).
5. Ability to give informed consent before the study initiation. Death patients and patients who are no longer contactable or lost to follow-up will be excluded from consent requirement.

Exclusion Criteria:

1. Pediatric patients.
2. Acute promyelocytic leukemia.

Primary outcomes:
measure: Percentage of patients with molecular alterations (FLT3 and NPM1 mutations).
timeFrame: Baseline
Secondary outcomes:
measure: Overall response rate.
timeFrame: Throughout the study period. Approximately 1 year
measure: Description of initial and later treatments in each baseline alterations studied (FLT3 and NPM1) in each AML type.
timeFrame: Baseline and throughout the study period. Approximately 1 year
measure: Molecular response rate.
timeFrame: Throughout the study period. Approximately 1 year
measure: Description of biology of disease at relapse or refractoriness by molecular characteristics.
timeFrame: Baseline and throughout the study period. Approximately 1 year
Other outcomes:
Locations:
city: Albacete
country: Spain
facility: Hospital General Universitario de Albacete
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol-ICO
city: Burgos
country: Spain
facility: Hospital Universitario de Burgos
city: Castellón De La Plana
country: Spain
facility: Hospital General Universitario de Castellón
city: Cáceres
country: Spain
facility: Hospital San Pedro de Alcántara
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofía
city: Las Palmas De Gran Canaria
country: Spain
facility: Hospital Universitario de Gran Canaria Doctor Negrín
city: León
country: Spain
facility: Hospital Universitario de León
city: Lugo
country: Spain
facility: Hospital Universitario Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Clínico San Carlos
city: Madrid
country: Spain
facility: Hospital Univeristario Ramón y Cajal
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Fundación Jiménez Díaz
city: Murcia
country: Spain
facility: Hospital General Universitario Morales Meseguer
city: Oviedo
country: Spain
facility: Hospital Universitario Central Asturias
city: Pamplona
country: Spain
facility: Clínica Universitaria de Navarra
city: Salamanca
country: Spain
facility: Hospital Universitario de Salamanca
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Clínico Universitario de Valencia
city: Valencia
country: Spain
facility: Hospital Universitari I Politécnic La Fe
city: Valencia
country: Spain
facility: Hospital Universitario Doctor Peset
Study officials:
affiliation: Hospital Universitari i Politècnic La Fe (Valencia)
name: Pau Montesinos Fernández
role: STUDY_CHAIR
References:
citation: Schlenk RF, Dohner K, Krauter J, Frohling S, Corbacioglu A, Bullinger L, Habdank M, Spath D, Morgan M, Benner A, Schlegelberger B, Heil G, Ganser A, Dohner H; German-Austrian Acute Myeloid Leukemia Study Group. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008 May 1;358(18):1909-18. doi: 10.1056/NEJMoa074306.
citation: Thiede C, Steudel C, Mohr B, Schaich M, Schakel U, Platzbecker U, Wermke M, Bornhauser M, Ritter M, Neubauer A, Ehninger G, Illmer T. Analysis of FLT3-activating mutations in 979 patients with acute myelogenous leukemia: association with FAB subtypes and identification of subgroups with poor prognosis. Blood. 2002 Jun 15;99(12):4326-35. doi: 10.1182/blood.v99.12.4326.
citation: Frohling S, Schlenk RF, Breitruck J, Benner A, Kreitmeier S, Tobis K, Dohner H, Dohner K; AML Study Group Ulm. Acute myeloid leukemia. Prognostic significance of activating FLT3 mutations in younger adults (16 to 60 years) with acute myeloid leukemia and normal cytogenetics: a study of the AML Study Group Ulm. Blood. 2002 Dec 15;100(13):4372-80. doi: 10.1182/blood-2002-05-1440. Epub 2002 Aug 8.
citation: Kottaridis PD, Gale RE, Frew ME, Harrison G, Langabeer SE, Belton AA, Walker H, Wheatley K, Bowen DT, Burnett AK, Goldstone AH, Linch DC. The presence of a FLT3 internal tandem duplication in patients with acute myeloid leukemia (AML) adds important prognostic information to cytogenetic risk group and response to the first cycle of chemotherapy: analysis of 854 patients from the United Kingdom Medical Research Council AML 10 and 12 trials. Blood. 2001 Sep 15;98(6):1752-9. doi: 10.1182/blood.v98.6.1752.
citation: Gale RE, Hills R, Kottaridis PD, Srirangan S, Wheatley K, Burnett AK, Linch DC. No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML10 and 12 trials. Blood. 2005 Nov 15;106(10):3658-65. doi: 10.1182/blood-2005-03-1323. Epub 2005 Aug 2.
citation: Rombouts WJ, Blokland I, Lowenberg B, Ploemacher RE. Biological characteristics and prognosis of adult acute myeloid leukemia with internal tandem duplications in the Flt3 gene. Leukemia. 2000 Apr;14(4):675-83. doi: 10.1038/sj.leu.2401731.
citation: Yokota S, Kiyoi H, Nakao M, Iwai T, Misawa S, Okuda T, Sonoda Y, Abe T, Kahsima K, Matsuo Y, Naoe T. Internal tandem duplication of the FLT3 gene is preferentially seen in acute myeloid leukemia and myelodysplastic syndrome among various hematological malignancies. A study on a large series of patients and cell lines. Leukemia. 1997 Oct;11(10):1605-9. doi: 10.1038/sj.leu.2400812.
citation: Whitman SP, Archer KJ, Feng L, Baldus C, Becknell B, Carlson BD, Carroll AJ, Mrozek K, Vardiman JW, George SL, Kolitz JE, Larson RA, Bloomfield CD, Caligiuri MA. Absence of the wild-type allele predicts poor prognosis in adult de novo acute myeloid leukemia with normal cytogenetics and the internal tandem duplication of FLT3: a cancer and leukemia group B study. Cancer Res. 2001 Oct 1;61(19):7233-9.
citation: Dohner K, Schlenk RF, Habdank M, Scholl C, Rucker FG, Corbacioglu A, Bullinger L, Frohling S, Dohner H. Mutant nucleophosmin (NPM1) predicts favorable prognosis in younger adults with acute myeloid leukemia and normal cytogenetics: interaction with other gene mutations. Blood. 2005 Dec 1;106(12):3740-6. doi: 10.1182/blood-2005-05-2164. Epub 2005 Jul 28.
citation: Verhaak RG, Goudswaard CS, van Putten W, Bijl MA, Sanders MA, Hugens W, Uitterlinden AG, Erpelinck CA, Delwel R, Lowenberg B, Valk PJ. Mutations in nucleophosmin (NPM1) in acute myeloid leukemia (AML): association with other gene abnormalities and previously established gene expression signatures and their favorable prognostic significance. Blood. 2005 Dec 1;106(12):3747-54. doi: 10.1182/blood-2005-05-2168. Epub 2005 Aug 18.
citation: Suzuki T, Kiyoi H, Ozeki K, Tomita A, Yamaji S, Suzuki R, Kodera Y, Miyawaki S, Asou N, Kuriyama K, Yagasaki F, Shimazaki C, Akiyama H, Nishimura M, Motoji T, Shinagawa K, Takeshita A, Ueda R, Kinoshita T, Emi N, Naoe T. Clinical characteristics and prognostic implications of NPM1 mutations in acute myeloid leukemia. Blood. 2005 Oct 15;106(8):2854-61. doi: 10.1182/blood-2005-04-1733. Epub 2005 Jun 30.
citation: Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner 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, Lowenberg 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.
citation: Hellmann F, Verdi M, Schlemper BR Jr, Caponi S. 50th anniversary of the Declaration of Helsinki: the double standard was introduced. Arch Med Res. 2014 Oct;45(7):600-1. doi: 10.1016/j.arcmed.2014.10.005. Epub 2014 Oct 31.