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

NCT02896842 | Completed Phase 2

• 1 other identifier: 09/38_ Optim Imatinib
• Study Type: interventional
• Target: 139
• Locations: 1 country
• Sites: 19

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.

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Outcome Measures

Primary Outcomes (1)

• The major molecular response rate at 12 months in cohort 1.

  12 months

Secondary Outcomes (9)

• Complete cytogenetic response at 6 and 12 months

  12 months

• Major molecular response rate at 12 months in cohort 2 and cohort 3.

  12 months

• Major molecular response at 3, 6, and 9 months

  9 months

• Complete molecular response 6 and 12 months

  12 months

• Relationship between plasmatic dosage and efficacy

  12 months

Study Arms (3)

Control Arm

NO INTERVENTION

cohort 3: Imatinib through dosage ≥ 1000 ng/ml

Active comparator

ACTIVE COMPARATOR

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

Other: active comparator

Experimental arm

EXPERIMENTAL

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

Drug: Posology dose modification

Interventions

Posology dose modification DRUG

Also known as: Cohort 1 : dose adjustment based on trough plasmatic

Experimental arm

active comparator OTHER

Also known as: Cohort 2 : Imatinib standard dose

Active comparator

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Versailles Hospital: lead

Study Sites (19)

CHU angers

Angers, France

Location

CH d'Annecy

Annecy, France

Location

CH argenteuil

Argenteuil, France

Location

CHU Bordeaux

Bordeaux, France

Location

Institut Bergonié

Bordeaux, France

Location

CH Boulogne

Boulogne, France

Location

CHU CAEN

Caen, France

Location

CH de Dieppe

Dieppe, France

Location

CH Dunkerque

Dunkirk, France

Location

CH Versailles

Le Chesnay, France

Location

CHU Lille

Lille, France

Location

CHU Lyon

Lyon, France

Location

CH Meaux

Meaux, France

Location

Hopital Bon secours

Metz, France

Location

CHU Nice

Nice, France

Location

Hopital La Source

Orléans La Source, France

Location

Hopital Necker

Paris, France

Location

CHU Rennes

Rennes, France

Location

Hopital Purpan

Toulouse, France

Location

Related Publications (1)

• Johnson-Ansah H, Maneglier B, Huguet F, Legros L, Escoffre-Barbe M, Gardembas M, Cony-Makhoul P, Coiteux V, Sutton L, Abarah W, Pouaty C, Pignon JM, Choufi B, Visanica S, Deau B, Morisset L, Cayssials E, Molimard M, Bouchet S, Mahon FX, Nicolini F, Aegerter P, Cayuela JM, Delord M, Bruzzoni-Giovanelli H, Rousselot P; Groupe Francais pour la LMC (Fi-LMC). Imatinib Optimized Therapy Improves Major Molecular Response Rates in Patients with Chronic Myeloid Leukemia. Pharmaceutics. 2022 Aug 12;14(8):1676. doi: 10.3390/pharmaceutics14081676.

  PMID: 36015302 RESULT

MeSH Terms

Conditions

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study coordonator

Study Record Dates

• First Submitted: September 7, 2016
• First Posted: September 12, 2016
• Study Start: September 1, 2010
• Primary Completion: March 1, 2015
• Study Completion: December 1, 2016
• Last Updated: July 6, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (19)