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Imatinib Mesylate

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Interruption of the treatment by Imatinib

Imatinib ending

François-Xavier MAHON, MD

The first purpose of this study is to evaluate the persistence of the complete molecular remission in patients with Chronic Myeloid Leukemia after stopping imatinib treatment (determine by Reverse Transcription real-time Polymerase Chain Reaction (RT-PCR) negative for bcr-abl transcripts). The second purpose is to determine clinicals and biologicals factors associated with the persistent complete molecular remission.

Principal Objective : To evaluate the complete molecular remission persistence after stopping imatinib during six months as measured by RT-PCR negative for bcr-abl transcripts in patients with Chronic Myeloid Leukemia .

Secondary Objective :

* To determine clinicals factors associated with complete molecular remission before and after stopping imatinib in patients with Chronic Myeloid Leukemia.
* To determine the biologics factors (immunologic and molecular) associated with complete molecular remission before and after stopping imatinib in patients with Chronic Myeloid Leukaemia.
* To determine the molecular relapse level after more than six month of persistent complete molecular remission without imatinib.
* To determine the complete molecular remission length.
* To evaluate medical and economical impact of stopping imatinib treatment.

Study design : multicentric trial

Evaluation of the Persistence of the Complete Molecular Remission After Stopping Imatinib Chronic Myeloid Leukemia

Evaluation of the Persistence of the Complete Molecular Remission After Stopping Imatinib Chronic Myeloid Leukemia (STIM)

University Hospital, Bordeaux

Imatinib stop

François-Xavier MAHON, Pr

Background: Complete molecular remission under imatinib, therapeutic interruption possible for patients in complete remission proved in different trials.

Purpose: Stopping imatinib in patients with chronic myeloid leukemia in complete molecular remission during two following years. The objectives of this study are to determine the rate of patients without a molecular relapse and so the rate of molecular relapse, to determine and to seek for clinical and biological CML-related factors predictive for a molecular relapse after imatinib discontinuation. These objectives require to increase the number of study patients to be enrolled for accurate statistical considerations. It will allow to predict which patients have to be proposed for discontinuation without risk of molecular relapse and to select the patients who need to continue or reinforce the treatment to achieve a complete long term eradication of the disease.

The gold standard for the treatment of chronic myeloid leukaemia (CML) is Imatinib, the first tyrosine inhibitor (TKI) of BCR-ABL. Imatinib specifically targets the BCR-ABL tyrosine kinase encoded by the BCR-ABL fusion gene, the molecular hallmark of CML. Regular monitoring of BCR-ABL transcript levels by quantitative RT-PCR is of key importance for the assessment of treatment response to imatinib.

Over time, an increasing proportion of imatinib-treated patients obtain a complete molecular response (CMR), defined as an undetectable molecular residual disease. In a previous study, STIM trial (PHRC 2006, stop Imatinib), 100 patients were included. The preliminary analysis among 69 patients having a median follow up of 21 months shows that the probability to maintain the CMR at 12 months is 45%. Our goal is actually to include up to 200 patients and then let the STIM opened during 3 years in a way to determine the predictive factors of the molecular relapse Discontinuation of treatment is proposed after checking selection criteria and signing informed consent. The assessment of BCR-ABL in peripheral blood by quantitative RT-PCR is performed every month during the first year then every two months second year then every three months during 3 years.

The molecular relapse after imatinib discontinuation is defined by positive PCR for BCR-ABL two times using RTQ-PCR with increasing of the transcript on two following assessment and or a value\> 0.1% i.e. lost of MMR. In case of molecular relapse it is recommended to re-challenge an imatinib treatment. According to our experience the 50 patients well documented who re challenged the treatment were sensitive again. The treatment of molecular relapse by second generation tyrosine kinase inhibitors (dasatinib or nilotinib) will possible in the current trial. It is important for all the French patients to be included in a national trial to avoid discontinuation without evaluation.

Multicenter Trial Estimating the Persistence of Molecular Remission in Chronic Myeloid Leukaemia in Long Term After Stopping Imatinib

Number of patients alive or died will be measured

The relevant clinical and biological factors which could be predictive of the the complete molecular remission persistence will be measured by dosage in the blood.

All adverse events will be reported to know what kind of adverse events occured to patients without treatment, number of patients with adverse events and in particular number of patients with lost of complete molecular remission.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Evaluation of the Persistence of the Complete Molecular Remission After Stopping Imatinib Chronic Myeloid Leukemia	NCT00478985	Myeloid Leukemi...	Imatinib ending	18 Years -	University Hospital, Bordeaux
Multicenter Trial Estimating the Persistence of Molecular Remission in Chronic Myeloid Leukaemia in Long Term After Stopping Imatinib	NCT01343173	Chronic Myeloid...	Imatinib stop	18 Years -	University Hospital, Bordeaux

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