Imatinib COncentration Monitoring Evaluation: the clinical usefulness of "routine" versus "rescue" therapeutic drug monitoring (TDM) interventions in chronic myeloid leukaemia (CML) patients

ISRCTN ISRCTN31181395
DOI https://doi.org/10.1186/ISRCTN31181395
EudraCT/CTIS number 2009-011519-19
Secondary identifying numbers EudraCT 2009-011519-19
Submission date
27/05/2009
Registration date
18/08/2009
Last edited
20/01/2015
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Cancer
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Study website

Contact information

Dr Thierry Buclin
Scientific

Division of Clinical Pharmacology and Toxicology
University Hospital Centre and University of Lausanne
Hopital Beaumont 06.633
Lausanne
1011
Switzerland

Phone +41 (0)21 314 42 60
Email Thierry.Buclin@chuv.ch

Study information

Study designMulticentre parallel group open-label randomised clinical trial
Primary study designInterventional
Secondary study designRandomised controlled trial
Study setting(s)Hospital
Study typeQuality of life
Participant information sheet Can be found at: http://www.imatinib-monitoring.ch/
Scientific titleA 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
Study acronymI-COME
Study objectivesCould 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(s)Faculty of Biology and Medicine Ethical Committee of the University of Lausanne approved on the 31st March 2009 (ref: CE 31/09)
Health condition(s) or problem(s) studiedChronic myeloid leukaemia (CML)
InterventionEach 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 typeOther
Primary outcome measure1. 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 measures1. 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 study start date31/03/2009
Completion date31/12/2012

Eligibility

Participant type(s)Patient
Age groupAdult
Lower age limit18 Years
SexBoth
Target number of participants300
Key inclusion criteria1. 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
Key exclusion criteria1. Pregnant and breastfeeding women are excluded de facto from this study
2. Less than 18 years of age
Date of first enrolment31/03/2009
Date of final enrolment31/12/2012

Locations

Countries of recruitment

  • Switzerland

Study participating centre

Division of Clinical Pharmacology and Toxicology
Lausanne
1011
Switzerland

Sponsor information

University Hospital Centre and University of Lausanne (CHUV) (Switzerland)
Hospital/treatment centre

Division of Clinical Pharmacology and Toxicology
Hopital Beaumont 06.633
Lausanne
1011
Switzerland

Website http://www.chuv.ch/
ROR logo "ROR" https://ror.org/05a353079

Funders

Funder type

Hospital/treatment centre

University Hospital Centre and University of Lausanne (CHUV) (Switzerland) - Division of Clinical Pharmacology and Toxicology

No information available

Novartis Switzerland, Bern (Switzerland) - received a grant in aid

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
Publication and dissemination planNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 01/12/2014 Yes No