A Prospective Randomized Phase II Study Evaluating the Monitoring of Imatinib Mesylate Plasmatic Through Level in Patients Newly Diagnosed With CP-CML

NCT ID: NCT02896842

Last Updated: 2017-11-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

139 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-09-30

Study Completion Date

2016-12-31

Brief Summary

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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.

Detailed Description

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Conditions

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Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Control Arm

cohort 3: Imatinib through dosage ≥ 1000 ng/ml

Group Type NO_INTERVENTION

No interventions assigned to this group

Active comparator

Cohort 2 : Imatinib standard dose Imatinib through dosage \< 1000 ng/ml

Group Type ACTIVE_COMPARATOR

active comparator

Intervention Type OTHER

Experimental arm

Cohort 1 : dose adjustment based on trough plasmatic level value Imatinib through dosage \< 1000 ng/ml

Group Type EXPERIMENTAL

Posology dose modification

Intervention Type DRUG

Interventions

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Posology dose modification

Intervention Type DRUG

active comparator

Intervention Type OTHER

Other Intervention Names

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Cohort 1 : dose adjustment based on trough plasmatic Cohort 2 : Imatinib standard dose

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Versailles Hospital

OTHER

Sponsor Role lead

Responsible Party

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Philippe ROUSSELOT

Study coordonator

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

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CHU angers

Angers, , France

Site Status

CH d'Annecy

Annecy, , France

Site Status

CH argenteuil

Argenteuil, , France

Site Status

CHU Bordeaux

Bordeaux, , France

Site Status

Institut Bergonié

Bordeaux, , France

Site Status

CH Boulogne

Boulogne, , France

Site Status

CHU CAEN

Caen, , France

Site Status

CH de Dieppe

Dieppe, , France

Site Status

CH Dunkerque

Dunkirk, , France

Site Status

CH Versailles

Le Chesnay, , France

Site Status

CHU Lille

Lille, , France

Site Status

CHU Lyon

Lyon, , France

Site Status

CH Meaux

Meaux, , France

Site Status

Hopital Bon secours

Metz, , France

Site Status

CHU Nice

Nice, , France

Site Status

Hopital La Source

Orléans La Source, , France

Site Status

Hopital Necker

Paris, , France

Site Status

CHU Rennes

Rennes, , France

Site Status

Hopital Purpan

Toulouse, , France

Site Status

Countries

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France

Other Identifiers

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09/38_ Optim Imatinib

Identifier Type: -

Identifier Source: org_study_id