The Efficacy of Therapy in Patients With Acute Myeloid Leukemia and Down Syndrome in Russia (AML-DS-2025)

Prospective Non-randomized Multicenter Trial: the Efficacy of Therapy in Patients With Acute Myeloid Leukemia and Down Syndrome in Russia

This prospective non-randomized multicenter trial created based on protocol ML DS 2006 and aimed at standardization of current therapy approaches and creating a national network for diagnostic, treatment and monitoring of children (0-18 years) with AML and Down syndrome in Russia. Based on the results the investigators expect to increase long-term overall and event-free survival in children with AML and DS and reduce the immediate and remote toxicity of chemotherapy by reducing the dose load of chemotherapeutic drugs.

The study protocol therapy for all patients includes four chemotherapy blocks:

Course 1 AIE (cytarabine/idarubicin/etoposide) Course 2 AI (cytarabine/idarubicin) Course 3 HAD (high -dose cytarabine (1g)/daunorubicin) Course 4 HA (high-dose cytarabine) Safety to be monitored based on CTCAE v5.0

Study Overview

• Status: Recruiting
• Conditions: Down Syndrome (DS); AML (Acute Myelogenous Leukemia)
• Intervention / Treatment: Drug: 4 chemotherapy blocks: Course 1 AIE (cytarabine/idarubicin/etoposide), Course 2 AI (cytarabine/idarubicin), Course 3 HAD (high-dose cytarabine (1g)/daunorubicin), Course 4 HA (high-dose cytarabine).

Detailed Description

This prospective non-randomized multicenter trial created based on protocol ML DS 2006 and aimed at standardization of current therapy approaches and creating a national network for diagnostic, treatment and monitoring of children (0-18 years) with AML and Down syndrome in Russia. Based on the results the investigators expect to increase long-term overall and event-free survival in children with AML and DS and reduce the immediate and remote toxicity of chemotherapy by reducing the dose load of chemotherapeutic drugs.

Patients to be included: Age 0-18 years

• Diagnosis of AML, MDS and presence of Down syndrome (constitutional trisomy 21 and mutation in the GATA1 gene)
• Signed informed consent

Patients not be included:

• Children with Down syndrome and acute lymphoblastic leukemia (ALL)
• Severe comorbidities with contraindications to the treatment according to the protocol
• Pre-treatment >14 days with intensive induction therapy
• Refusal of all therapy or important elements of therapy

NB: Patients with Transient Abnormal Myelopoiesis (TAM) are eligible for enrollment but will be included in the analysis as a separate group.

Patients with M7 AML, trisomy 21 in the tumor clone (without the Down syndrome phenotype) and mutation in the GATA1 gene should be discussed individually with the protocol group to determine the treatment strategy, as patients with M7 AML and trisomy 21 in tumor clone (without the Down syndrome phenotype) are not included in current version of pediatric AML clinical recommendations.

If a patient meets the inclusion criteria, but cannot/should not receive treatment according to the protocol, he/she can be enrolled in the study as a patient under observation. The results of therapy of patients under observation will not be taken into account in the assessment of treatment efficacy.

The study protocol therapy for all patients includes four chemotherapy blocks:

Course 1 AIE (cytarabine/idarubicin/etoposide) Course 2 AI (cytarabine/idarubicin) Course 3 HAD (high-dose cytarabine (1g)/daunorubicin) Course 4 HA (high-dose cytarabine)/ Efficacy parameters include Response rate; event-free survival (EFS); relapse-free survival (RFS); overall survival (OS); treatment-related mortality, myelogram, MRD Safety to be monitored based on CTCAE v5.0 The AML-DS-2025 protocol does not include a maintenance therapy course in order to reduce toxicity and improve quality of life.

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Zalina A Abashidze, MD; Phone Number: 89661101770; Email: zalina.abashidze@dgoi.ru

Study Locations

• Russia
  • Moscow, Russia
    • Recruiting
    • National medical research center of pediatric haematology, oncology and immulogy named after Dmytriy Rogachyov, Moscow, 117198
    • Contact: Lena f Smirnova; Phone Number: +7(985)130-61-03; Email: lena.smirnova@dgoi.ru

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 0-18 years
• Diagnosis of AML, MDS and presence of Down syndrome (constitutional trisomy 21 and mutation in the GATA1 gene)
• Signed informed consent

Exclusion Criteria:

• Children with Down syndrome and acute lymphoblastic leukemia (ALL)
• Severe comorbidities with contraindications to the treatment according to the protocol
• Pre-treatment >14 days with intensive induction therapy
• Refusal of all therapy or important elements of therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: 4 chemotherapy blocks: cytarabine/idarubicin/etoposide, cytarabine/idarubicin, high-dose cytarabine

Drug: 4 chemotherapy blocks: Course 1 AIE (cytarabine/idarubicin/etoposide), Course 2 AI (cytarabine/idarubicin), Course 3 HAD (high-dose cytarabine (1g)/daunorubicin), Course 4 HA (high-dose cytarabine).; 4 chemotherapy blocks: Course 1 AIE (cytarabine/idarubicin/etoposide), Course 2 AI (cytarabine/idarubicin), Course 3 HAD (high-dose cytarabine (1g)/daunorubicin), Course 4 HA (high-dose cytarabine).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
event-free survival	Response rate; event-free survival (EFS)	up to 2 years
relapse-free survival (RFS)		up to 2 years
overall survival (OS)		up to 2 years
treatment-related mortality		up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CTCAE	Number of adverse events by Common Terminology Criteria for Adverse Events (CTCAE) 5.0	up to 2 years

Collaborators and Investigators

• Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Study record dates

Study Major Dates

• Study Start (Actual): July 24, 2025
• Primary Completion (Estimated): July 24, 2030
• Study Completion (Estimated): December 30, 2032

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Estimated): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): November 20, 2025
• Last Update Submitted That Met QC Criteria: November 17, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: AML; Down Syndrome; Acute Myelogenous Leukemia; DS
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Neoplasms; Genetic Diseases, Inborn; Neoplasms by Histologic Type; Neurobehavioral Manifestations; Hematologic Diseases; Congenital Abnormalities; Leukemia, Myeloid; Abnormalities, Multiple; Intellectual Disability; Leukemia; Chromosome Disorders; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Leukemia, Myeloid, Acute; Down Syndrome; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Arabinonucleosides; Anthracyclines; Naphthacenes; Aminoglycosides; Cytarabine; Etoposide; Daunorubicin; Idarubicin
• Other Study ID Numbers: NCHPOI- 2025-8

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No