Plain English Summary
Not provided at time of registration
Trial website
Contact information
Type
Scientific
Primary contact
Dr Thierry Buclin
ORCID ID
Contact details
Division of Clinical Pharmacology and Toxicology
University Hospital Centre and University of Lausanne
Hopital Beaumont 06.633
Lausanne
1011
Switzerland
+41 (0)21 314 42 60
Thierry.Buclin@chuv.ch
Additional identifiers
EudraCT number
2009-011519-19
ClinicalTrials.gov number
Protocol/serial number
EudraCT 2009-011519-19
Study information
Scientific title
A study to compare the clinical usefulness of "routine" versus "rescue" therapeutic drug monitoring (TDM) interventions in chronic myeloid leukaemia (CML) patients: a multicentre parallel group open-label randomised clinical trial
Acronym
I-COME
Study hypothesis
Could a routine therapeutic drug monitoring (TDM) program of imatinib improve the clinical outcome of chronic myeloid leukaemia (CML) patients treated with imatinib (i.e. good quality of life achieved by an event free survival and lack of moderate clinical or severe laboratory adverse events), compared with a rescue recourse to TDM reserved to problematic cases (i.e. suboptimal achievement of therapeutic response or suspicion of toxicity)?
Ethics approval
Faculty of Biology and Medicine Ethical Committee of the University of Lausanne approved on the 31st March 2009 (ref: CE 31/09)
Study design
Multicentre parallel group open-label randomised clinical trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Quality of life
Patient information sheet
Can be found at: http://www.imatinib-monitoring.ch/
Condition
Chronic myeloid leukaemia (CML)
Intervention
Each patient will achieve a one-year study period while being included in one of the two following groups:
Intervention arm:
A systematic monitoring of imatinib plasma concentrations will be performed starting from study inclusion and during the whole observation period, in order to optimise the dosage regimen. Initially, up to 3 cycles of TDM-based adjustments will serve to normalise trough plasma levels around a target of 1000 ng/ml. Since no consensual upper limit of blood level has been defined for imatinib, a dosage reduction will be primarily driven by the clinical situation and will only be proposed in case of signs of toxicity (grade 2 or 3, as defined in the primary endpoint) along with a trough plasma level significantly higher than 1000 ng/ml. The trough level will also be measured at this time in order to document a possible high imatinib concentration. Measurement of blood concentration and dosage re-adjustment will remain accessible throughout the study in case of clinical concerns ("rescue TDM").
Control arm:
The patients will continue to be treated according to the standard of care for CML (i.e. ELN recommendations), without routine measurement of imatinib concentrations. Measurement of blood concentration will however be possible in case of clinical concerns ("rescue TDM") for either unsatisfactory therapeutic response or occurrence of toxicity. However, no access to TDM determinations will be granted on introduction of interacting drugs. In the absence of clinical concerns, the control patients will simply provide two blood samples (one at inclusion, and one after 1 year of treatment), which are planned to be measured by the laboratory only at the end of the study.
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measures
1. Percentage of patients remaining without lack of efficacy or disease progression (i.e. "event-free" according to IRSI study definition)
2. Occurrence of moderate or severe adverse events (NCI-CTC grade 2 or more oedema, fatigue, headache, nausea, diarrhoea, musculoskeletal pain and skin rash; grade 3 or more anaemia, neutropenia, thrombocytopenia and increased liver enzymes; leucopenia and vomiting will not be analysed because of their obvious correlation with neutropenia and nausea)
3. Discontinuation of treatment
Measured after one-year follow-up.
Secondary outcome measures
1. Percentage of patients achieving major molecular response (MMR) after one-year follow-up
2. Median reduction of BCR-ABL transcripts (i.e. molecular response) over one year
3. Percentage of patients achieving complete cytogenetic response (CCyR) after one-year follow-up
4. Percentage of patients remaining without moderate adverse events of any kind (NCI-CTC grade 2)
5. Percentage of patients with clinical concerns at inclusion (i.e. lack of response/progression or adverse events) and presenting an improvement over one year
6. Percentage of patients with imatinib plasma levels above 1000 ng/ml after one-year follow-up
7. Predictive performance of either total or free concentrations for the achievement of therapeutic outcomes or the occurrence of concentration-related adverse effects (PK-PD relationships using all collected samples)
8. Interaction of genetic factors or co-medication known to affect drug transport (P-gp and hOCT1) and metabolism (CYP3A) with pharmacokinetic variables and efficacy/toxicity outcomes
9. Compliance of practitioners towards dosage adaptation advice
Overall trial start date
31/03/2009
Overall trial end date
31/12/2012
Reason abandoned
Eligibility
Participant inclusion criteria
1. CML patients in the chronic or accelerated phase of the disease
2. Receiving imatinib since less than 5 years
3. Aged 18 years and older, either sex
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
300
Participant exclusion criteria
1. Pregnant and breastfeeding women are excluded de facto from this study
2. Less than 18 years of age
Recruitment start date
31/03/2009
Recruitment end date
31/12/2012
Locations
Countries of recruitment
Switzerland
Trial participating centre
Division of Clinical Pharmacology and Toxicology
Lausanne
1011
Switzerland
Sponsor information
Organisation
University Hospital Centre and University of Lausanne (CHUV) (Switzerland)
Sponsor details
Division of Clinical Pharmacology and Toxicology
Hopital Beaumont 06.633
Lausanne
1011
Switzerland
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Hospital/treatment centre
Funder name
University Hospital Centre and University of Lausanne (CHUV) (Switzerland) - Division of Clinical Pharmacology and Toxicology
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Funder name
Novartis Switzerland, Bern (Switzerland) - received a grant in aid
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Results - basic reporting
Publication summary
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25297989