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

NCT03846362

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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

Clinical Trial IDs

  • ORG STUDY ID: NCPHOI-2018-05
  • NCT ID: NCT03846362

Conditions

  • Acute Myeloid Leukemia, Childhood

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
intermediate risk MRD2>0,1%ExperimentalMRD2>0,1% - FLA - MRD3 - HSCT

    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.
          
    Maximum Eligible Age:18 Years
    Minimum Eligible Age:N/A
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:relapse-free survival (RFS)
    Time Frame:1 year
    Safety Issue:
    Description: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

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

    Details

    Phase:Phase 3
    Primary Purpose:Interventional
    Overall Status:Not yet recruiting
    Lead Sponsor:Federal Research Institute of Pediatric Hematology, Oncology and Immunology

    Trial Keywords

    • AML
    • MRD
    • stem cell transplantation
    • pediatric
    • leukemia
    • haploidentical
    • TcRab-depletion
    • young adult

    Last Updated