Back to resultsPhase III Trial Evaluating the Effectiveness of a Dose Adjustment of Imatinib Mesylate on the Molecular Response (MIM)
Primary Purpose
Leukemia, Myeloid, Chronic-Phase
Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Imatinib Mesylate 600 MG Oral Tablet
Imatinib Mesylate 400 MG Oral Tablet
Imatinib Mesylate
Sponsored by
About this trial
This is an interventional treatment trial for Leukemia, Myeloid, Chronic-Phase focused on measuring chronic myeloid leukemia in chronic phase, residual plasma IM concentration, adapted strategy
Eligibility Criteria
Inclusion Criteria:
- Patients with CML-CP treated for at least two years by Imatinib Mesylate 400 mg / d,
- Patients in complete cytogenetic response for at least 1 year
- Patients with residual disease detectable by quantitative RT-PCR (RQ-PCR)
- ECOG ≤ 2,
- Age ≥ 18 years
- Signed informed consent,
- Membership of a social security system
Exclusion Criteria:
- Patients with CML-CP Philadelphia chromosome negative diagnosis.
- Patients previously treated with Imatinib Mesylate at doses above 400 mg / day
- Patient with non-hematologic toxicity of grade III or IV in Imatinib Mesylate 400mg / d
- Patient with a medical condition endocrine, psychiatric, neurological, renal, hepatic or cardiac progressive uncontrolled by medical treatment
- Pregnant or breastfeeding women, women of childbearing potential not using a contraceptive method effective
- Known HIV positive
- Patients previously treated with another tyrosine kinase inhibitor
- Patient participating in another interventional clinical trial
- History of non-compliance to Imatinib Mesylate
Sites / Locations
- Institut Bergonié
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Other
Arm Label
Imatinib 600 (Randomized trial)
Imatinib 400 (Randomized trial)
Imatinib400 (Cohort)
Arm Description
Randomized Cohort: Adapted strategy of dosage of Imatinib Mesylate : 600mg/d po
Randomized Cohort: Standard strategy of dosage of Imatinib Mesylate : 400mg/d po
Parallel Cohort: Standard strategy of dosage of Imatinib Mesylate : 400mg/d po
Outcomes
Primary Outcome Measures
Percentage of Patients Presenting a Decline of the BCR-ABL Transcript Rate at 12 Months From Baseline - Randomised Study
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
Rate of Decline of 2-log of the BCR-ABL Transcript Rate at 3 ,6, 9 and 12 Months From Baseline - Randomised Study
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
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)
Time to complete molecular response was defined by the time from inclusion/randomization and the first CMR.
Rate of BCR-ABL Undetectable
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
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.
Overall Survival
Overall survival is defined by the time from de date of inclusion/randomization to the date of death (of any cause).
Progression-free Survival
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).
Full Information
NCT ID
NCT01827930
First Posted
November 5, 2012
Last Updated
December 30, 2020
Sponsor
Institut Bergonié
Collaborators
Novartis
1. Study Identification
Unique Protocol Identification Number
NCT01827930
Brief Title
Phase III Trial Evaluating the Effectiveness of a Dose Adjustment of Imatinib Mesylate on the Molecular Response
Acronym
MIM
Official Title
Phase III Trial Evaluating the Effectiveness of a Dose Adjustment of IM on the Molecular Response in Patients With LMC in Chronic Phase Treated With IM 400 mg / Day for at Least Two Years, Complete Cytogenetic Response for at Least One Year
Study Type
Interventional
2. Study Status
Record Verification Date
December 2020
Overall Recruitment Status
Terminated
Why Stopped
Difficulties of enrolment of Patient
Study Start Date
July 2009 (Actual)
Primary Completion Date
January 1, 2017 (Actual)
Study Completion Date
January 1, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut Bergonié
Collaborators
Novartis
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Myeloid, Chronic-Phase
Keywords
chronic myeloid leukemia in chronic phase, residual plasma IM concentration, adapted strategy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
IM concentration < 1000ng/mL Randomized Cohort : "adapted strategy" versus "standard strategy" / IM concentration >= 1000ng/mL Parallel Cohort: "standard strategy"
Masking
None (Open Label)
Allocation
Randomized
Enrollment
68 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Imatinib 600 (Randomized trial)
Arm Type
Experimental
Arm Description
Randomized Cohort: Adapted strategy of dosage of Imatinib Mesylate : 600mg/d po
Arm Title
Imatinib 400 (Randomized trial)
Arm Type
Active Comparator
Arm Description
Randomized Cohort: Standard strategy of dosage of Imatinib Mesylate : 400mg/d po
Arm Title
Imatinib400 (Cohort)
Arm Type
Other
Arm Description
Parallel Cohort: Standard strategy of dosage of Imatinib Mesylate : 400mg/d po
Intervention Type
Drug
Intervention Name(s)
Imatinib Mesylate 600 MG Oral Tablet
Other Intervention Name(s)
GLIVEC
Intervention Description
Imatinib Mesylate for CP CML
Intervention Type
Drug
Intervention Name(s)
Imatinib Mesylate 400 MG Oral Tablet
Other Intervention Name(s)
GLIVEC
Intervention Description
Imatinib Mesylate for CP CML
Intervention Type
Drug
Intervention Name(s)
Imatinib Mesylate
Other Intervention Name(s)
GLIVEC
Intervention Description
Imatinib Mesylate for CP CML
Primary Outcome Measure Information:
Title
Percentage of Patients Presenting a Decline of the BCR-ABL Transcript Rate at 12 Months From Baseline - Randomised Study
Description
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.
Time Frame
12 months
Secondary Outcome Measure Information:
Title
Rate of Decline of 2-log of the BCR-ABL Transcript Rate at 3 ,6, 9 and 12 Months From Baseline - Randomised Study
Description
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).
Time Frame
3, 6, 9 and 12 months
Title
Molecular Response at 3, 6, 9 and 12 Months
Description
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 Frame
3, 6, 9 and 12 months
Title
Time to Complete Molecular Response (CMR) and Major Molecular Response (MMR)
Description
Time to complete molecular response was defined by the time from inclusion/randomization and the first CMR.
Time Frame
From date of randomization until the date of complete molecular response (up to 12 months)
Title
Rate of BCR-ABL Undetectable
Description
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 Frame
12 first months
Title
Time to the First BCR-ABL Undetectable
Description
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.
Time Frame
within 12 months following randomization
Title
Overall Survival
Description
Overall survival is defined by the time from de date of inclusion/randomization to the date of death (of any cause).
Time Frame
First 12 months
Title
Progression-free Survival
Description
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).
Time Frame
First 12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with CML-CP treated for at least two years by Imatinib Mesylate 400 mg / d,
Patients in complete cytogenetic response for at least 1 year
Patients with residual disease detectable by quantitative RT-PCR (RQ-PCR)
ECOG ≤ 2,
Age ≥ 18 years
Signed informed consent,
Membership of a social security system
Exclusion Criteria:
Patients with CML-CP Philadelphia chromosome negative diagnosis.
Patients previously treated with Imatinib Mesylate at doses above 400 mg / day
Patient with non-hematologic toxicity of grade III or IV in Imatinib Mesylate 400mg / d
Patient with a medical condition endocrine, psychiatric, neurological, renal, hepatic or cardiac progressive uncontrolled by medical treatment
Pregnant or breastfeeding women, women of childbearing potential not using a contraceptive method effective
Known HIV positive
Patients previously treated with another tyrosine kinase inhibitor
Patient participating in another interventional clinical trial
History of non-compliance to Imatinib Mesylate
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ETIENNE Gabriel, MD
Organizational Affiliation
Institut Bergonié
Official's Role
Study Chair
Facility Information:
Facility Name
Institut Bergonié
City
Bordeaux
State/Province
Aquitaine
ZIP/Postal Code
33000
Country
France
12. IPD Sharing Statement
Links:
URL
https://www.e-cancer.fr/Professionnels-de-sante/Le-registre-des-essais-cliniques
Description
Registre des essais cliniques de l'INCa
URL
https://www.bergonie.fr/les-essais-cliniques
Description
Site internet du promoteur, l'Institut Bergonié
Learn more about this trial
Phase III Trial Evaluating the Effectiveness of a Dose Adjustment of Imatinib Mesylate on the Molecular Response
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