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

Leukemia, Myeloid, Chronic-Phase Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01827930
• Other study ID #: IB2009-07
• Secondary ID: 2008-007094-20
• Status: Terminated
• Phase: Phase 3
• Start date: July 2009
• Est. completion date: January 1, 2017

Study information

• Verified date: December 2020
• Source: Institut Bergonié
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 68
• Est. completion date: January 1, 2017
• Est. primary completion date: January 1, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• Imatinib Mesylate 600 MG Oral Tablet
Imatinib Mesylate for CP CML
• Imatinib Mesylate 400 MG Oral Tablet
Imatinib Mesylate for CP CML
• Imatinib Mesylate
Imatinib Mesylate for CP CML

Locations

Country	Name	City	State
France	Institut Bergonié	Bordeaux	Aquitaine

Sponsors (2)

Lead Sponsor	Collaborator
Institut Bergonié	Novartis

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	12 months
Secondary	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).	3, 6, 9 and 12 months
Secondary	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.	3, 6, 9 and 12 months
Secondary	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.	From date of randomization until the date of complete molecular response (up to 12 months)
Secondary	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.	12 first months
Secondary	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.	within 12 months following randomization
Secondary	Overall Survival	Overall survival is defined by the time from de date of inclusion/randomization to the date of death (of any cause).	First 12 months
Secondary	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).	First 12 months

External Links

•   Registre des essais cliniques de l'INCa
•   Site internet du promoteur, l'Institut Bergonié