Brief Summary

Acute myeloid leukemia (AML) is a clonal neoplastic disease of the hematopoietic tissue associated with a mutation in the precursor cell of hematopoiesis, which results in a differentiation block and uncontrolled proliferation of immature myeloid cells. Anthracycline antibiotics have been an integral part of the treatment of acute myeloid leukemia since the 1970s. However, the clinical usefulness of anthracyclines is limited primarily by the high incidence of cardiotoxicity. According to the European Society of Cardiology guidelines for cardio-oncology, cardiovascular toxicity is defined as any impairment of cardiac function associated with anticancer treatment, as the term encompasses both a wide range of possible clinical manifestations and an etiological relationship with various treatments, including chemotherapy, radiation therapy, immunotherapy and treatment with targeted drugs. Cardiovascular toxicity can be acute, subacute or delayed, manifesting many years after chemotherapy or radiation therapy, involving a number of cardiac structures, which can lead to the development of heart failure, coronary heart disease, valvular heart disease, arrhythmias, including cardiac conduction disorders and diseases of the pericardium. Anthracycline-induced cardiotoxicity is the negative effect of anthracyclines on normal cardiac activity due to their toxic effects on the heart muscle and the cardiac conduction system. Anthracycline-induced cardiotoxicity manifests as asymptomatic left ventricular dysfunction in 57% of treated patients and restrictive or dilated cardiomyopathy leading to congestive heart failure (CHF) in 16% to 20% of patients. Anthracycline-induced congestive heart failure is often resistant to therapy and has a mortality rate of up to 79%. Thus, there is a need for early detection of cardiovascular dysfunction associated with chemotherapy treatment of acute myeloid leukemia in order to timely prescribe drug therapy. Purpose of the study To optimize the early detection of endothelial dysfunction and left ventricular myocardial contractility in patients with acute myeloid leukemia during chemotherapy treatment based on a comprehensive assessment of instrumental and laboratory research parameters. Expected results Based on a comprehensive analysis using laser Doppler flowmetry, stress echocardiography with the determination of global longitudinal strain of the myocardium, biochemical markers of endothelial damage and cardiac biomarkers, a correlation between violations of the contractility of the left ventricular myocardium and violations of the vasoregulatory function of the vascular endothelium will be revealed, which will allow developing an algorithm for early detection of cardiomyopathy and vascular complications in patients with acute myeloid leukemia during chemotherapy treatment.

Trial Health

Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date

Enrollment

100

participants targeted

Target at P50-P75 for not_applicable

Timeline

Completed

Started Dec 2022

Typical duration for not_applicable

Geographic Reach

1 country

1 active site

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

2.7 years study duration

Study Start

First participant enrolled

December 1, 2022

Completed

18 days until next milestone

First Submitted

Initial submission to the registry

December 19, 2022

Completed

1 month until next milestone

First Posted

Study publicly available on registry

January 27, 2023

Completed

1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2025

Completed

7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 3, 2025

Completed

Last Updated

November 5, 2024

Status Verified

October 1, 2024

Enrollment Period

2.1 years

First QC Date

December 19, 2022

Last Update Submit

November 2, 2024

Conditions

Acute Myeloid Leukemia, Adult Cardiotoxicity Endothelial Dysfunction

Keywords

Acute Myeloid LeukemiaCardiotoxicityEndothelial DysfunctionPolychemotherapyAnthracyclines

Outcome Measures

Primary Outcomes (1)

Change of global longitudinal strain of 15% or more relative to the initial values
Change of global longitudinal strain of the myocardium according to stress echocardiography by 15% or more relative to the values obtained before the start of chemotherapy treatment.
Evaluation is carried out within 1 week after each course of chemotherapy up to 10 months, evaluated after each course of induction of remission and consolidation of remission.

Secondary Outcomes (6)

Change of the index of microcirculation according to laser Doppler flowmetry
Evaluation is carried out within 1 week after each course of chemotherapy up to 10 months, evaluated after each course of induction of remission and consolidation of remission.
Change of the Coefficient of Variation of Microcirculation According to Laser Doppler Fluometry
Evaluation is carried out within 1 week after each course of chemotherapy up to 10 months, evaluated after each course of induction of remission and consolidation of remission.
Change of the level of highly sensitive T-troponin
Evaluation is carried out within 1 week after each course of chemotherapy up to 10 months, evaluated after each course of induction of remission and consolidation of remission.
Change of brain natriuretic peptide level
Evaluation is carried out within 1 week after each course of chemotherapy up to 10 months, evaluated after each course of induction of remission and consolidation of remission.
Change of the level of asymmetric dimethylarginine
Evaluation is carried out within 1 week after each course of chemotherapy up to 10 months, evaluated after each course of induction of remission and consolidation of remission.
+1 more secondary outcomes

Study Arms (2)

The study group

OTHER

The study group will include patients with acute myeloid leukemia receiving chemotherapy, aged 18 to 65 years, without clinical signs of heart failure, with an LV ejection fraction of more than 50% before the start of polychemotherapy, in whom in the course of chemotherapy treatment after the next course of treatment a decrease in global longitudinal strain of 15% or more relative to the initial values will be revealed.

Diagnostic Test: History takingDiagnostic Test: AnthropometryDiagnostic Test: Complete blood countDiagnostic Test: Biochemical blood testDiagnostic Test: CoagulogramDiagnostic Test: Immunoenzymatic analysis of the level of endothelin-1, asymmetric dimethylarginineDiagnostic Test: Stress echocardiography with the definition of global longitudinal deformation of the myocardiumDiagnostic Test: Triplex scanning of neck vesselsDiagnostic Test: ElectrocardiographyDiagnostic Test: Ultrasound of the abdominal cavity (with calculation of the area of the spleen) and lymph nodesDiagnostic Test: Cytogenetic examination of the bone marrow to determine genetic abnormalities.Diagnostic Test: Cytological examination of bone marrow cells with cytochemical examinationDiagnostic Test: Immunophenotypic examination of the bone marrow by flow cytometryDiagnostic Test: Determination of the presence of a FLT3 mutation using the PCR MethodDiagnostic Test: laser Doppler flowmetry

The control group

OTHER

The control group will consist of patients with acute myeloid leukemia receiving chemotherapy, aged 18 to 65 years, without clinical signs of heart failure, with an LV ejection fraction of more than 50% before the start of polychemotherapy, in whom no signs of myocardial disease will be detected during chemotherapy. and endothelial dysfunction.

Interventions

History takingDIAGNOSTIC_TEST

Careful history taking, including using questionnaires, to identify risk factors for the development of cardiovascular diseases using the SCORE scale.