A Prospective Multicenter Clinical Trial of MRD-based Treatment Strategy in Children and Young Adults With AML
- Conditions
- Acute Myeloid Leukemia, Childhood
- Interventions
- Other: HSCT
- Registration Number
- NCT03846362
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
- de novo acute myeloid leukemia
- signed informed consent
diagnosis of: Fanconi anemia, acute promyelocytic leukemia, MDS, JMML, AML as secondary malignancy, Dawn syndrome.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description intermediate risk MRD2>0,1% HSCT MRD2\>0,1% - FLA - MRD3 - HSCT
- Primary Outcome Measures
Name Time Method relapse-free survival (RFS) 1 year relapse-free survival from date of diagnosis till date of relapse, or date of death (whichever comes first) or date of last follow up
- Secondary Outcome Measures
Name Time Method overall survival (OS) 1 year event-free survival (EFS) 2 years Event=relapse/nonresponse, death or second malignancy
The proportion of of patients with severe adverse effects 6 months The proportion of of patients with severe adverse effects of therapy according to CTCAE (ver 4.3)
The proportion of of patients with severe infections 1 month The proportion of of patients with severe infections: number of episodes, grade, after each course of chemotherapy
The proportion of of patients with severe cardiotoxicity 1 year The proportion of of patients with severe cardiotoxicity: number of episodes and %EF by echocardiogam
MRD dynamic 1 months MRD (IFT and/or PCR) dynamic between check-points
MRD specificity and sensitivity 1, 2, 3 months MRD specificity and sensitivity in relapse prognosis
Cumulative incidence of relapse 6 months, 1 year competing event - death in CR
Cumulative incidence of transplant-related mortality 6 months after HSCT for transplanted patients
Cumulative incidence of aGvHD II-IV grade 100 days after HSCT for transplanted patients
Cumulative incidence of cGvHD 1 year after HSCT for transplanted patients
Trial Locations
- Locations (2)
Dmitry Rogachev National Research Center of Pediatric Hematology, Oncology and Immunology
🇷🇺Moscow, Russian Federation
Regional Children's Clinical Hospital â„– 1
🇷🇺Ekaterinburg, Sverdlovsk Oblast, Russian Federation