A Prospective Multicenter Clinical Trial of MRD-based Treatment Strategy in Children and Young Adults With AML

Acute Myeloid Leukemia, Childhood Clinical Trial

Official title:

A Prospective Multicenter Clinical Trial of Treatment Strategy Based on MRD Level After 2 Initial Courses of Chemotherapy in Children and Young Adults With Acute Myeloid Leukemia

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03846362
• Other study ID #: NCPHOI-2018-05
• Status: Recruiting
• Phase: Phase 3
• Start date: April 1, 2019
• Est. completion date: January 2025

Study information

• Verified date: March 2023
• Source: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
• Contact: Irina Kalinina
• Phone: +7 495 287 65 70
• Email: oml-registration[@]fnkc.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Minimal-residual disease (MRD) will be measured either by flow cytometry, or polymerase chain reaction (PCR) methods, in 3 check-points and it will be one of the decision-making control parameter for the optimal therapy tactics.

Patients with initially high-risk group and those with high MRD after 2 initial courses of chemotherapy will be assigned to the allogenic transplantation of the hematopoietic stem cells from Human Leucocyte Antigen (HLA) matched or haploidentical family donors.

Description:

Genetic alterations in acute myeloid leukemia (AML) clone are well known prognostic risk factors of AML relapse. Standard risk group includes favorable t (15;17) (q22; q21) and inv (16)/t (16;16). High-risk patients have a complex karyotype rearrangement (3 and more), inversion of the long arm in 3rd chromosome and EVI1 gene rearrangement, monosomy 5 and 7, translocations involving KMT2A gene and several rare translocations. All other genotype alterations attributed to the moderate risk group.

Besides genetic factors, detection of the minimal residual disease (MRD) after initial chemotherapy and its decrease rate after 1st postremission chemotherapy with high dose Cytarabine and anthracyclines, plays a crucial role in the development of the morphologic relapse. Patients with PCR-MRD<0,1% after 2 courses of chemotherapy have a 30% or less risk of relapse, while PCR-MRD>0,1% - over 70%. In the clinical trial investigators are planning to measure MRD either by immune-phenotype, or PCR methods, in 3 check-points and it will be one of decision-making control parameter for the optimal therapy tactics.

Patients with initially high-risk group and those with high MRD after 2 initial courses of chemotherapy will be assigned to the allogenic transplantation of the hematopoietic stem cells from HLA- matched or haploidentical family donors.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: January 2025
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 18 Years

Eligibility

Inclusion Criteria:

1. de novo acute myeloid leukemia

2. signed informed consent

Exclusion Criteria:

diagnosis of: Fanconi anemia, acute promyelocytic leukemia, MDS, JMML, AML as secondary malignancy, Dawn syndrome.

Related Conditions & MeSH terms

• Acute Myeloid Leukemia, Childhood
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Other:
• HSCT
allogenic HSCT from 5-8 HLA-MM family donor as a first choice for patients with initial high risk of relapse and for patients with MRD2>0,1% and initial intermediate risk

Locations

Country	Name	City	State
Russian Federation	Regional Children's Clinical Hospital ? 1	Ekaterinburg	Sverdlovsk Oblast
Russian Federation	Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology	Moscow

Sponsors (2)

Lead Sponsor	Collaborator
Federal Research Institute of Pediatric Hematology, Oncology and Immunology	Physicians, Innovations, Science for Children Fund

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	relapse-free survival (RFS)	relapse-free survival from date of diagnosis till date of relapse, or date of death (whichever comes first) or date of last follow up	1 year
Secondary	overall survival (OS)		1 year
Secondary	event-free survival (EFS)	Event=relapse/nonresponse, death or second malignancy	2 years
Secondary	The proportion of of patients with severe adverse effects	The proportion of of patients with severe adverse effects of therapy according to CTCAE (ver 4.3)	6 months
Secondary	The proportion of of patients with severe infections	The proportion of of patients with severe infections: number of episodes, grade, after each course of chemotherapy	1 month
Secondary	The proportion of of patients with severe cardiotoxicity	The proportion of of patients with severe cardiotoxicity: number of episodes and %EF by echocardiogam	1 year
Secondary	MRD dynamic	MRD (IFT and/or PCR) dynamic between check-points	1 months
Secondary	MRD specificity and sensitivity	MRD specificity and sensitivity in relapse prognosis	1, 2, 3 months
Secondary	Cumulative incidence of relapse	competing event - death in CR	6 months, 1 year
Secondary	Cumulative incidence of transplant-related mortality	for transplanted patients	6 months after HSCT
Secondary	Cumulative incidence of aGvHD II-IV grade	for transplanted patients	100 days after HSCT
Secondary	Cumulative incidence of cGvHD	for transplanted patients	1 year after HSCT