Condition category
Cancer
Date applied
27/05/2009
Date assigned
18/08/2009
Last edited
20/01/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

http://www.imatinib-monitoring.ch/

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

http://www.chuv.ch/

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

Publication citations

Additional files

Editorial Notes