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

Leukemia, Myelogenous, Chronic, BCR-ABL Positive Clinical Trial

— OPTIMIMATINIB  

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02896842
• Other study ID #: 09/38_ Optim Imatinib
• Status: Completed
• Phase: Phase 2
• First received: September 7, 2016
• Last updated: November 21, 2017
• Start date: September 2010
• Est. completion date: December 2016

Study information

• Verified date: November 2017
• Source: Versailles Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 139
• Est. completion date: December 2016
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Leukemia, Myeloid
• Leukemia, Myeloid, Chronic-Phase

Intervention

Drug:
• Posology dose modification

Other:
• active comparator

Locations

Country	Name	City	State
France	CHU angers	Angers
France	CH d'Annecy	Annecy
France	CH argenteuil	Argenteuil
France	CHU Bordeaux	Bordeaux
France	Institut Bergonié	Bordeaux
France	CH Boulogne	Boulogne
France	CHU CAEN	Caen
France	CH de Dieppe	Dieppe
France	CH Dunkerque	Dunkerque
France	CH Versailles	Le Chesnay
France	CHU Lille	Lille
France	CHU Lyon	Lyon
France	CH Meaux	Meaux
France	Hopital Bon secours	Metz
France	CHU Nice	Nice
France	Hopital La Source	Orléans La Source
France	Hopital Necker	Paris
France	CHU Rennes	Rennes
France	Hopital Purpan	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
Versailles Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The major molecular response rate at 12 months in cohort 1.		12 months
Secondary	Complete cytogenetic response at 6 and 12 months		12 months
Secondary	Major molecular response rate at 12 months in cohort 2 and cohort 3.		12 months
Secondary	Major molecular response at 3, 6, and 9 months		9 months
Secondary	Complete molecular response 6 and 12 months		12 months
Secondary	Relationship between plasmatic dosage and efficacy		12 months
Secondary	Relationship between plasmatic dosage and tolerance		12 months
Secondary	Progression free survival		5 years
Secondary	Event free survival		5 years
Secondary	Overall survival		5 years