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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Acute Myeloid Leukemia, Childhood
• Intervention / Treatment: Other: HSCT

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 500
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Irina Kalinina; Phone Number: 7425 +7 495 287 65 70; Email: oml-registration@fnkc.ru
• Study Contact Backup: Name: Zhanna Shekhovtsova; Phone Number: 7538 +7 495 287 65 70; Email: zhanna.shekhovtsova@fccho-moscow.ru

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 117198
    • Recruiting
    • Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
    • Contact: Irina Kalinina; Phone Number: 7432 84956647078; Email: oml-registration@fnkc.ru
    • Contact: Zhanna Shekhovtsova; Phone Number: 84956647078; Email: zhanna.shekhovtsova@fccho-moscow.ru
  • Sverdlovsk Oblast
    • Ekaterinburg, Sverdlovsk Oblast, Russian Federation, 620149
      • Not yet recruiting
      • Regional Children's Clinical Hospital № 1
      • Contact: Oleg Arakaev; Phone Number: (343) 231-91-09
      • Principal Investigator: Larisa Fechina, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

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
Experimental: intermediate risk MRD2>0,1%; MRD2>0,1% - FLA - MRD3 - HSCT	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival (OS)		1 year
event-free survival (EFS)	Event=relapse/nonresponse, death or second malignancy	2 years
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
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
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
MRD dynamic	MRD (IFT and/or PCR) dynamic between check-points	1 months
MRD specificity and sensitivity	MRD specificity and sensitivity in relapse prognosis	1, 2, 3 months
Cumulative incidence of relapse	competing event - death in CR	6 months, 1 year
Cumulative incidence of transplant-related mortality	for transplanted patients	6 months after HSCT
Cumulative incidence of aGvHD II-IV grade	for transplanted patients	100 days after HSCT
Cumulative incidence of cGvHD	for transplanted patients	1 year after HSCT

Collaborators and Investigators

• Sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
• Collaborators: Physicians, Innovations, Science for Children Fund
• Investigators: Principal Investigator: Alexey Maschan, National Research Center for Pediatric Hematology , Moscow, Russian Federation; Study Director: Michael Maschan, National Research Center for Pediatric Hematology , Moscow, Russian Federation; Study Chair: Galina Novichkova, National Research Center for Pediatric Hematology , Moscow, Russian Federation

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2019
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): January 1, 2025

Study Registration Dates

• First Submitted: February 14, 2019
• First Submitted That Met QC Criteria: February 18, 2019
• First Posted (Actual): February 19, 2019

Study Record Updates

• Last Update Posted (Actual): March 16, 2023
• Last Update Submitted That Met QC Criteria: March 15, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: pediatric; young adult; stem cell transplantation; AML; leukemia; MRD; haploidentical; TcRab-depletion
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: NCPHOI-2018-05

Drug and device information, study documents

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