Phase III Trial Evaluating the Effectiveness of a Dose Adjustment of Imatinib Mesylate on the Molecular Response

Phase 3

Terminated

• Conditions: Leukemia, Myeloid, Chronic-Phase
• Interventions: Drug: Imatinib Mesylate 600 MG Oral Tablet; Drug: Imatinib Mesylate 400 MG Oral Tablet; Drug: Imatinib Mesylate

• Registration Number: NCT01827930
• Lead Sponsor: Institut Bergonié

Brief Summary

The Imatinib Mesylate at a dose of 400 mg / day is the standard treatment for patients with CML-CP. Recent studies show that the quality of response rate (complete cytogenetic response and major molecular response rate) is dependent on the residual plasma Imatinib.

Detailed Description

The Imatinib Mesylate at a dose of 400 mg / day is the standard treatment for patients with CML-CP. Recent studies show that the quality of response rate (complete cytogenetic response and major molecular response rate) is dependent on the residual plasma Imatinib. This study aims to evaluate the effectiveness of a strategy for dose adjustment of Imatinib Mesylate based on the measurement of the residual plasma imatinib in patients treated for at least 2 years Imatinib 400 mg / d in complete cytogenetic response for at least 1 year.

Study Timeline

• Study Start: 2009-07
• Study First Submitted: 2012-11-05
• Study First Submitted QC: 2013-04-09
• Study First Posted: 2013-04-10
• Primary Completion: 2017-01-01
• Study Completion: 2017-01-01
• Results First Submitted: 2020-10-15
• Status Verified: 2020-12
• Results First Submitted QC: 2020-12-30
• Last Update Submitted: 2020-12-30
• Results First Posted: 2020-12-31
• Last Update Posted: 2020-12-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

1. Patients with CML-CP treated for at least two years by Imatinib Mesylate 400 mg / d,
2. Patients in complete cytogenetic response for at least 1 year
3. Patients with residual disease detectable by quantitative RT-PCR (RQ-PCR)
4. ECOG ≤ 2,
5. Age ≥ 18 years
6. Signed informed consent,
7. Membership of a social security system

Exclusion Criteria

1. Patients with CML-CP Philadelphia chromosome negative diagnosis.
2. Patients previously treated with Imatinib Mesylate at doses above 400 mg / day
3. Patient with non-hematologic toxicity of grade III or IV in Imatinib Mesylate 400mg / d
4. Patient with a medical condition endocrine, psychiatric, neurological, renal, hepatic or cardiac progressive uncontrolled by medical treatment
5. Pregnant or breastfeeding women, women of childbearing potential not using a contraceptive method effective
6. Known HIV positive
7. Patients previously treated with another tyrosine kinase inhibitor
8. Patient participating in another interventional clinical trial
9. History of non-compliance to Imatinib Mesylate

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Imatinib 600 (Randomized trial)	Imatinib Mesylate 600 MG Oral Tablet	Randomized Cohort: Adapted strategy of dosage of Imatinib Mesylate : 600mg/d po
Imatinib 400 (Randomized trial)	Imatinib Mesylate 400 MG Oral Tablet	Randomized Cohort: Standard strategy of dosage of Imatinib Mesylate : 400mg/d po
Imatinib400 (Cohort)	Imatinib Mesylate	Parallel Cohort: Standard strategy of dosage of Imatinib Mesylate : 400mg/d po

Primary Outcome Measures

Name	Time	Method
Percentage of Patients Presenting a Decline of the BCR-ABL Transcript Rate at 12 Months From Baseline - Randomised Study	12 months	The BCR-ABL transcript rate was analysed by molecular biology by RQ-PCR at study entry, 3 months, 6 months, 9 months and 12 months.; Treatment is considered effective at 12 months if: * for patients with an inclusion transcript rate less than 0.1%: the transcript rate at 12 months is less or equal to 0.001% or undetectable.; * for patients with an inclusion transcript rate greater than 0.1% : the transcript rate at 12 months is less or equal to 0.1% or undetectable.; If BCR-ABL transcript level was unavailable at M12, the treatment was considered ineffective.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	First 12 months	Overall survival is defined by the time from de date of inclusion/randomization to the date of death (of any cause).
Progression-free Survival	First 12 months	Progression-free survival was defined by the time from the date of inclusion and the date of progression.; Progression was defined as : * Death,; * Passage into the acceleration phase defined by one of the following criteria: % of blood or medullary blasts greater than 15% but less than 30%, blasts plus promyelocytes greater than 30% in the blood or marrow, basophils greater than 20% in the blood, thrombocytopenia less than 100x10\^9/L unrelated to treatment, clonal evolution); * Passage to the blast transformation phase defined by one of the following criteria: % of blasts of blood or bone marrow greater than 30%, occurrence of extramedullary damage other than histologically proven hepato-splenic.; * Increase in BCR-ABL transcripts greater than or equal to 2-log compared to the previous values (this increase must be confirmed within 3 months).
Rate of BCR-ABL Undetectable	12 first months	The BCR-ABL transcript rate was analysed by molecular biology by RQ-PCR at study entry, 3 months, 6 months, 9 months and 12 months.
Rate of Decline of 2-log of the BCR-ABL Transcript Rate at 3 ,6, 9 and 12 Months From Baseline - Randomised Study	3, 6, 9 and 12 months	The BCR-ABL transcript rate was analysed by molecular biology by RQ-PCR at study entry, 3 months, 6 months, 9 months and 12 months.; Efficacy was also evaluated at 3, 6, 9 and 12 months in terms of decreasing the rate of BCR-ABL transcripts of 2 logarithms, relative to the initial value (inclusion). The lack of data on the transcript rate was considered as failure (no decrease).
Molecular Response at 3, 6, 9 and 12 Months	3, 6, 9 and 12 months	The molecular response is defined by the measurement of BCR-ABL transcript rate by quantitative RT-PCR (RQ-PCR) on peripheral venous blood according to international standards.; It is defined as: * Major Molecular Response (MMR): BRC-ABL transcript rate ≤ 0.1%; * Complete Molecular Response (CMR): transcript BCR-ABL undetectable and non quantifiable.
Time to Complete Molecular Response (CMR) and Major Molecular Response (MMR)	From date of randomization until the date of complete molecular response (up to 12 months)	Time to complete molecular response was defined by the time from inclusion/randomization and the first CMR.
Time to the First BCR-ABL Undetectable	within 12 months following randomization	The BCR-ABL transcript rate was analysed by molecular biology by RQ-PCR at study entry, 3 months, 6 months, 9 months and 12 months.; Time to the first BCR-ABL undetectable was defined by the time from inclusion/randomization and the first CMR.

Trial Locations

Locations (1)

Institut Bergonié; 🇫🇷 Bordeaux, Aquitaine, France