Chronic myeloid leukaemia MedDRA version: 16.0 Level: LLT Classification code 10009015 Term: Chronic myeloid leukemia System Organ Class: 100000004864 MedDRA version: 16.0 Level: LLT Classification code 10009016 Term: Chronic myeloid leukemia in remission System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Glivec
Product Name: Imatinib
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: imatinib
Concentration unit: mg m
Sponsors
University of Liverpool
Royal Liverpool and Broagreen University Hospitals NHS Trust
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) CML in first chronic phase. 2) Demonstration of BCR-ABL1 positivity at or shortly after original diagnosis*. 3) Written Informed Consent 4) Must have received TKI treatment for at least 3 years. 5) At least 3 molecular results over the preceding 12 months, that fit either of the following groups (results from any UK lab are acceptable): a)(MR4 group) all the available BCR-ABL1 molecular results over the preceding 12 months are in MR4 (MR4 is defined as a BCR-ABL1/ABL1 ratio of zero, with at least 10,000 ABL1 control transcripts). b)(MMR group) some or all BCR-ABL1 molecular results are in MMR (BCR-ABL1/ABL1 ratio of 0.1% or less, but not zero, with at least 10,000 ABL1 control transcripts). If the results over the preceding 12 months are a mix of MMR and undetectable BCR-ABL1, then the patient is eligible for the MMR but not the MR4 group. * Patients who are Philadelphia chromosome (Ph) negative (or whose Ph status is not known) are eligible. Patients who do not have a standard BCR-ABL1 fusion transcript (i.e. other than e13a2 or e14a2, also known as b2a2 and b3a2) are eligible, but before screening the patient, contact should be made with Prof Foroni at Imperial College (see contacts) since specialised quantitative molecular assessment will be required. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 100 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 68
Exclusion criteria
Exclusion criteria: 1)Age under 18 2)Life expectancy is predicted to be less than 37 months because of intercurrent illness 3)Presence of serious concomitant illness (e.g. heart, renal, respiratory or active malignant disease) that might preclude completion of the study 4)CML in accelerated phase or blast crisis at any time 5)Any molecular result during the preceding 12 months that is not in either MMR or MR4. 6)Treatment with higher than standard TKI doses (‘standard’ is defined as imatinib 400mg daily, nilotinib 400mg twice daily or dasatinib 100mg daily) 7)Patients who switched previous licensed TKI treatment (imatinib, nilotinib or dasatinib) twice or more because of intolerance. 8)Patients who switched previous licensed TKI treatment (imatinib, nilotinib or dasatinib) because of resistance. 9)Patients treated with lower than standard TKI doses (imatinib 400mg daily, nilotinib 400mg twice daily or dasatinib 100mg daily) for tolerance reasons may be included, but will de-escalate to the same doses as for standard dose patients and will be analysed separately, as they could be seen as undertreated. 10)Previous treatment with ponatinib or bosutinib. Patients who received interferon prior to commencing TKI (even if resistant to their interferon) are eligible, provided their response to TKI fits the entry criteria. 11)Pregnant or lactating women 12) Women of childbearing potential, including women whose last menstrual period was less than one year prior to screening, unable or unwilling to use adequate contraception from study start to one year after the last dose of protocol therapy. Adequate contraception is defined as hormonal birth control, intrauterine device, double barrier method or total abstinence.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary endpoint of the study is the proportion of patients who lose MMR during the trial observation period of 37 months. BCR-ABL1 will be assessed by standard PCR based molecular monitoring on blood. This is a routine part of clinical follow-up, but will be carried out more frequently than usual. It is not expected that any patient will undergo more serious relapse than loss of MMR, so there are no formal plans for routine marrow examinations. MR4 and MMR patients will receive the same strategy, but will be analysed separately.;Secondary Objective: The other questions being asked are: 1) If treatment is decreased/stopped, patient well-being might be expected to improve as treatment-related side effects are ameliorated. However, this could be offset by anxiety about the increased molecular surveillance (‘PCRitis’). An important aspect of the study is therefore serial Quality of Life assessments. These will be carried out using standard EQ-5D and FACT-BRM questionnaires at monthly intervals initially, decreasing subsequently. 2) Health Economic assessment will be included to assess the overall cost effectiveness of the strategy. 3) Associated laboratory based projects will address biological features which might characterise patients who can safely discontinue treatment. 4) Proportion of patients who can successfully de-escalate their treatment (to half the standard dose of their TKI), but who then lose MMR on complete TKI cessation 5) Proportion of patients who lose their MMR on de-escalation/stopping and regain MM;Primary end point(s): The primary endpoint of the study is the proportion of patients who lose MMR during the trial observation period of 37 months.;Timepoint(s) of evaluation of this end point: During the 37 months of follow-up | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The other questions being asked are: 1) If treatment is decreased/stopped, patient well-being might be expected to improve as treatment-related side effects are ameliorated. However, this could be offset by anxiety about the increased molecular surveillance (‘PCRitis’). An important aspect of the study is therefore serial Quality of Life assessments. These will be carried out using standard EQ-5D and FACT-BRM questionnaires at monthly intervals initially, decreasing subsequently. 2) Health Economic assessment will be included to assess the overall cost effectiveness of the strategy. 3) Associated laboratory based projects will address biological features which might characterise patients who can safely discontinue treatment.;Timepoint(s) of evaluation of this end point: During the 37 months of follow-up. | — |
Countries
United Kingdom
Outcome results
None listed