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.
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
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.