Clinical trial NCT02896842: A Prospective Randomized Phase II Study Evaluating the Monitoring of Imatinib Mesylate Plasmatic Through Level in Patients Newly Diagnosed With CP-CML
Official title: A Prospective Randomized Phase II Study Evaluating the Monitoring of Imatinib Mesylate (Glivec®) Plasmatic Through Level in Patients Newly Diagnosed With Chronic Phase Chronic Myelogenous Leukaemia (CP-CML).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lead sponsor: Versailles Hospital
Sponsor class: OTHER
First posted: 2016-09-12
Enrollment: 139
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Imatinib mesylate (Gleevec/Glivec, IM) is currently the gold standard or CML-CP front line therapy. The recommended dose of IM is 400 mg/day. The rates of complete cytogenetic responses at 3, 6 and 12 months are 27%, 50% and 69% respectively. The optimal IM daily dose is not yet determined and randomized studies addressing this question are on-going. First results from the TOPS trial (EHA 2008 congress) suggest a more rapid kinetic of response for patients treated with imatinib high dose. Recent studies revealed that initial Imatinib plasmatic dosage is predictive for achieving complete cytogenetic responses (CCR) and that a dosage of 1000 ng/ml is associated with a higher proportion of major molecular responses (MMR) (Picard et al., Blood 2007, Larson et al. Blood 2007).

Results from the study of Larson et al. indicate that around 40% of the patients had a trough plasmatic level below 1000 ng/ml after day 28 of imatinib 400 mg/d. The major molecular response rate at 12 months for the patients with the lower plasmatic through level is 25.4% compared to 40.1% for the patients with a plasmatic dosage over 800 to 1000 ng/ml.

Investigators propose to adapt the imatinib daily dose in case of imatinib through plasmatic level at day 28 below 1000 ng/ml. Patients with a trough plasmatic dosage ≤ 1000 ng/ml will be randomized between a prospective adaptation strategy of the imatinib daily dose (cohort 1) versus observation only (cohort 2). The patients with adequate imatinib dosage (\> 1000 ng/ml) will be followed up according the ELN recommendation (cohort 3). Imatinib trough plasmatic level will then be rechecked every month thereafter for patients in cohort 1 and cohort 2 and every three months in cohort 3. The first endpoint of the study will be the rate of major molecular response at 12 months in cohort 1. Our hypothesis is to improve the 12 months MMR rate with the optimized strategy (cohort 1) from 25% of MMR at 12 months to 40% of MMR at 12 months.


Eligibility criteria: Inclusion Criteria:

1. Male or female patient ≥ 18 years
2. Philadelphia chromosome positive newly diagnosed chronic myelogenous leukaemia (≤ 4 months) in first chronic phase.
3. Not previously treated with tyrosine kinase inhibitors other than imatinib
4. Prior treatment with imatinib during less than 13 weeks
5. Signed written inform consent
6. Women of childbearing potential (WOCBP) must be using an adequate method of contraception

Exclusion Criteria:

1. Patients with BCR-ABL positive, Philadelphia negative CML
2. Patient previously treated with TKI other than imatinib
3. Pregnancy
4. Active malignancy
5. Concurrent severe diseases which exclude the administration of therapy

Primary outcomes:
measure: The major molecular response rate at 12 months in cohort 1.
timeFrame: 12 months
Secondary outcomes:
measure: Complete cytogenetic response at 6 and 12 months
timeFrame: 12 months
measure: Major molecular response rate at 12 months in cohort 2 and cohort 3.
timeFrame: 12 months
measure: Major molecular response at 3, 6, and 9 months
timeFrame: 9 months
measure: Complete molecular response 6 and 12 months
timeFrame: 12 months
measure: Relationship between plasmatic dosage and efficacy
timeFrame: 12 months
measure: Relationship between plasmatic dosage and tolerance
timeFrame: 12 months
measure: Progression free survival
timeFrame: 5 years
measure: Event free survival
timeFrame: 5 years
measure: Overall survival
timeFrame: 5 years
Other outcomes:
Locations:
city: Angers
country: France
facility: CHU angers
city: Annecy
country: France
facility: CH d'Annecy
city: Argenteuil
country: France
facility: CH argenteuil
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Bordeaux
country: France
facility: Institut Bergonié
city: Boulogne
country: France
facility: CH Boulogne
city: Caen
country: France
facility: CHU CAEN
city: Dieppe
country: France
facility: CH de Dieppe
city: Dunkerque
country: France
facility: CH Dunkerque
city: Le Chesnay
country: France
facility: CH Versailles
city: Lille
country: France
facility: CHU Lille
city: Lyon
country: France
facility: CHU Lyon
city: Meaux
country: France
facility: CH Meaux
city: Metz
country: France
facility: Hopital Bon secours
city: Nice
country: France
facility: CHU Nice
city: Orléans La Source
country: France
facility: Hopital La Source
city: Paris
country: France
facility: Hopital Necker
city: Rennes
country: France
facility: CHU Rennes
city: Toulouse
country: France
facility: Hopital Purpan
Study officials:
References: