Clinical Trials /

Treatment Modification Based on Early Assessment of CML Patients

NCT01762969

Description:

The investigators will check the feasibility of using early molecular response for making treatment decisions. Patients diagnosed with chronic myeloid leukemia will commence imatinib treatment. After 3 months of treatment their response will be assessed. If molecular response would be less the 10% (BCR-ABL1/ABL ISI >10%)imatinib therapy will be stopped and patients will start a different TKI (as nilotinib, dasatinib). The investigators will follow on lab and clinical outcomes.

Related Conditions:
  • Chronic Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Treatment Modification Based on Early Assessment of CML Patients
  • Official Title: Modification of Imatinib to Other Tyrosine Kinase Inhibitors Dependent on 3-months Molecular Response of CML Patients

Clinical Trial IDs

  • ORG STUDY ID: CML-IS001
  • NCT ID: NCT01762969

Conditions

  • CML

Purpose

The investigators will check the feasibility of using early molecular response for making treatment decisions. Patients diagnosed with chronic myeloid leukemia will commence imatinib treatment. After 3 months of treatment their response will be assessed. If molecular response would be less the 10% (BCR-ABL1/ABL ISI >10%)imatinib therapy will be stopped and patients will start a different TKI (as nilotinib, dasatinib). The investigators will follow on lab and clinical outcomes.

Detailed Description

      Objectives:

      To establish a national protocol for the treatment of patients with CML. Patients will be
      stratified by molecular response, and treatment will be adjusted accordingly.

      Secondary outcomes To compare clinical outcomes of patients at high risk (transcript level
      above 10%) to those at low risk (<10%) while using the early switch approach To evaluate the
      prognostic value of EUTOS, HASFORD, and SOKAL scores using the early switch strategy Patients
      Patients may be enrolled to the protocol prior to any TKI treatment or at any time point from
      commencement of imatinib (started at 400 mg daily) and prior to 3 months assessment, if all
      the necessary baseline data is available, and all other inclusion criteria are met (patients
      will be excluded if they received treatment with a tyrosine kinase inhibitor other than
      imatinib)

      Inclusion criteria:

        1. Adult patients within 6 months after the diagnosis of Philadelphia chromosome-positive
           CML in the chronic phase

             1. who were not previously treated (with the exception of hydroyurea) for CML or

             2. who were treated with imatinib for CML for up to 3 months, and prior to 3 months
                assessment (patients will be excluded if they received treatment with a tyrosine
                kinase inhibitor other than imatinib).

        2. Age > 18 years Diagnosis of CML will be made by conventional cytogenetic (chromosome
           banding analysis) and/or interphase fluorescent in situ hybridization (FISH) analysis of
           bone marrow containing at least one Philadelphia chromosome-positive metaphase cell. If
           BCR-ABL1 fusion gene (Philadelphia chromosome) is not detected by conventional
           cytogenetic analysis, the diagnosis of CML can be confirmed based on FISH analysis or
           molecular analysis (demonstration of bcr-abl by polymerase chain reaction (PCR)).

      Inclusion of patients with any organ dysfunction (cardiac, renal, respiratory, liver) can be
      done based on the decision of the treating physician.

      Exclusion criteria:

      Patients will be excluded if they received treatment with a tyrosine kinase inhibitor other
      than imatinib (i.e., nilotinib, dasatinib) before study entry. Patients may take hydroxyurea
      or anagrelide for up to 4 weeks prior to imatinib treatment.

      Interventions Imatinib 400 mg once daily Response will be assessed after 3 months of therapy.
      A complete blood count to assess hematologic response and a bone marrow biopsy and/or
      aspirate, including cytogenetic analysis and molecular analysis for quantitative RT-PCR for
      BCR-ABL1/ABL will be performed.

      Response assessment Assessment of response by molecular analysis of bcr-abl1 will be
      performed in certified and standardized laboratories (a list of certified laboratories will
      be distributed).

      If a patients has achieved CHR and BCR-ABL1/ABL ISI <10% at 3 months then imatinib will be
      continued at the dose of 400 mg daily.

      If a patient has achieved CHR and BCR-ABL1/ABL ISI >10% at 3 months then imatinib will be
      stopped and nilotinib 300 mg twice daily or dasatinib 100 mg once daily will be instituted.
      ECG will be done prior to any change of therapy.

      Mutation analysis is recommended prior to the commencement of nilotinib or dasatinib.

      Patients will continue to receive the study treatment until the disease will progress or
      unacceptable toxic effects will developed. In the event of disease progression or the
      occurrence of adverse event treatment can be stopped or changed under the discretion of the
      treating physician.

      Outcomes Rate of CCyR at 12 months CCyR is defined as absence of Ph-positive metaphases,
      determined on the basis of G-banding in at least 20 cells in metaphase per bone marrow sample
      Overall survival Rate of major molecular response at 6, 12, 18, 24 months Cumulative rate of
      optimal response at 12, 18 months

      PFS:

      Time from commencement of imatinib till meeting ELN criteria for failure, progression to
      AP/BC, or death from any cause

      EFS:

      Time from commencement of imatinib till meeting ELN criteria for failure, progression to
      AP/BC, grade 3 to 4 adverse event, drug discontinuation (except of the change of imatinib at
      3 months according to molecular response), or death from any cause

      Safety:

      Adverse events will be classified according to the CTCAE NCI US v.3.0 Severe AE
    

Trial Arms

NameTypeDescriptionInterventions
Modified by molecular responseExperimentalPatients will be treated with imatinib upon diagnosis of CML. Molecular response will be assessed at 3 months of therapy. Based on molecular response imatinib will be continued or changed to another TKI

    Eligibility Criteria

            Inclusion Criteria:
    
              -  1. Adult patients within 6 months after the diagnosis of Philadelphia
                 chromosome-positive CML in the chronic phase
    
                   1. who were not previously treated (with the exception of hydroyurea) for CML or
    
                   2. who were treated with imatinib for CML for up to 3 months, and prior to 3 months
                      assessment (patients will be excluded if they received treatment with a tyrosine
                      kinase inhibitor other than imatinib).
    
                      2. Age > 18 years Diagnosis of CML will be made by conventional cytogenetic
                      (chromosome banding analysis) and/or interphase fluorescent in situ hybridization
                      (FISH) analysis of bone marrow containing at least one Philadelphia
                      chromosome-positive metaphase cell. If BCR-ABL1 fusion gene (Philadelphia
                      chromosome) is not detected by conventional cytogenetic analysis, the diagnosis
                      of CML can be confirmed based on FISH analysis or molecular analysis
                      (demonstration of bcr-abl by polymerase chain reaction (PCR)).
    
                      Inclusion of patients with any organ dysfunction (cardiac, renal, respiratory,
                      liver) can be done based on the decision of the treating physician.
    
                      Exclusion Criteria:
    
                      Patients will be excluded if they received treatment with a tyrosine kinase
                      inhibitor other than imatinib (i.e., nilotinib, dasatinib) before study entry.
                      Patients may take hydroxyurea or anagrelide for up to 4 weeks prior to imatinib
                      treatment.
          
    Maximum Eligible Age:N/A
    Minimum Eligible Age:16 Years
    Eligible Gender:All
    Healthy Volunteers:No

    Primary Outcome Measures

    Measure:Rate of complete cytogenetic response
    Time Frame:12 months
    Safety Issue:
    Description:

    Secondary Outcome Measures

    Measure:Overall survival
    Time Frame:12 months
    Safety Issue:
    Description:
    Measure:Rate of major molecular response
    Time Frame:12, 24 months
    Safety Issue:
    Description:Cumulative rate of optimal response at 12, 18 months
    Measure:PFS
    Time Frame:12 months
    Safety Issue:
    Description:Time from commencement of imatinib till meeting ELN criteria for failure, progression to AP/BC, or death from any cause
    Measure:Severe Adverse events
    Time Frame:12 months
    Safety Issue:
    Description:Adverse events will be classified according to the CTCAE NCI US v.3.0

    Details

    Phase:Phase 2
    Primary Purpose:Interventional
    Overall Status:Recruiting
    Lead Sponsor:Rabin Medical Center

    Last Updated