Clinical trial NCT03846362: A Prospective Multicenter Clinical Trial of MRD-based Treatment Strategy in Children and Young Adults With AML
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Acute Myeloid Leukemia, Childhood
Keywords: AML
MRD
stem cell transplantation
pediatric
leukemia
haploidentical
TcRab-depletion
young adult
Lead sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Sponsor class: OTHER
Collaborators: name: Physicians, Innovations, Science for Children Fund
First posted: 2019-02-19
Enrollment: 500
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: relapse-free survival (RFS)
timeFrame: 1 year
Secondary outcomes:
measure: overall survival (OS)
timeFrame: 1 year
measure: event-free survival (EFS)
timeFrame: 2 years
measure: The proportion of of patients with severe adverse effects
timeFrame: 6 months
measure: The proportion of of patients with severe infections
timeFrame: 1 month
measure: The proportion of of patients with severe cardiotoxicity
timeFrame: 1 year
measure: MRD dynamic
timeFrame: 1 months
measure: MRD specificity and sensitivity
timeFrame: 1, 2, 3 months
measure: Cumulative incidence of relapse
timeFrame: 6 months, 1 year
measure: Cumulative incidence of transplant-related mortality
timeFrame: 6 months after HSCT
measure: Cumulative incidence of aGvHD II-IV grade
timeFrame: 100 days after HSCT
measure: Cumulative incidence of cGvHD
timeFrame: 1 year after HSCT
Other outcomes:
Locations:
city: Ekaterinburg
country: Russian Federation
facility: Regional Children's Clinical Hospital № 1
state: Sverdlovsk Oblast
city: Moscow
country: Russian Federation
facility: Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
Study officials:
affiliation: National Research Center for Pediatric Hematology , Moscow, Russian Federation
name: Alexey Maschan
role: PRINCIPAL_INVESTIGATOR
affiliation: National Research Center for Pediatric Hematology , Moscow, Russian Federation
name: Michael Maschan
role: STUDY_DIRECTOR
affiliation: National Research Center for Pediatric Hematology , Moscow, Russian Federation
name: Galina Novichkova
role: STUDY_CHAIR
References: