- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01343173
Multicenter Trial Estimating the Persistence of Molecular Remission in Chronic Myeloid Leukaemia in Long Term After Stopping Imatinib (STIM 2)
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.
Study Overview
Detailed Description
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.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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-
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Angers, France, 49033
- University Hospital Angers
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Annecy, France
- CH Annecy
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Besançon, France
- CHU Bensançon
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Bordeaux, France, 33076
- Institut Bergonie
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Brest, France, 29285
- Hôpital Morvan
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Caen, France
- CHU Caen
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Colmar, France, 68000
- Hôpitaux Civils de Colmar
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Corbeil-Essonnes, France
- CH SUd Francilien
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Creteil, France, 94000
- Hopital Henri-Mondor
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Grenoble, France, 38043
- CHU Grenoble
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La Roche Sur Yon, France, 85025
- Centre Hospitalier - La Roche sur Yon
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Lille, France, 59037
- Lille University hospital - Hôpital Claude Huriez
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Limoges, France
- CHU Dupuytren
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Lyon, France, 69374
- Hôpital Edouard HERRIOT
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Marseille, France, 13273
- Institut Paoli Calmette
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Nantes, France, 44035
- CHU Hôtel-Dieu
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Nevers, France, 58033
- Centre Hospitalier de Nevers
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Nice, France, 06202
- CHU de Nice - Hôpital Archet 1
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Paris, France, 75475
- Hôpital Saint Louis
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Paris, France, 75743
- Hôpital Necker-Enfants Malades
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Pessac, France, 33604
- University Hospital Bordeaux, Hôpital du Haut Lévêque
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Poitiers, France, 86021
- University Hospital Poitiers - Hôpital Jean Bernard
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Rennes, France, 35033
- Hôpital Pontchaillou
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Rouen, France
- Centre Henri Becquerel
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Saint Brieuc, France
- CH Yves Le Foll
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Saint Pierre, France
- CH Régional de l'ILE DE LA REUNION/ Groupe Hospitalier Sud
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Saint-Denis, France, 97405
- CHR La Réunion
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Toulouse, France, 31059
- Hopital Purpan
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Valence, France
- CH Valence
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Vandoeuvre Les Nancy, France, 54500
- C.H.U. Brabois
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Vannes, France
- CH Bretagne Atlantique
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Versailles, France, 78157
- Centre Hospitalier de Versailles - Hopital Andre Mignot
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 18 years and older.
- Chronic myeloid leukaemia in chronic or accelerated phase under treatment with imatinib for at least 3 years.
- Complete molecular remission under treatment with imatinib for at least 2 years.
- HIV serology negative and absence of chronic hepatitis B or C.
- Molecular monitoring according to the international recommendations before the beginning of the study
- For the women old enough to procreate, method of effective contraception
- All patients must be informed of the investigational nature of this study and must sign and give written informed consent.
Exclusion Criteria:
- Under 18 years old.
- Pregnant at the inclusion's time.
- Hospitalized patients without consent.
- Adults under law protection or without ability to assent.
- Previous or planned allogeneic stem cell transplantation.
- HIV serology positive or chronic hepatitis B or C.
- Interfering treatment (corticosteroids, immunosuppressors, chemotherapy, radiotherapy).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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EXPERIMENTAL: Patients
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To stop imatinib after inclusion.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Rate of molecular relapse defined by the rate of patients having a significant increasing of BCR-ABL transcript.
Time Frame: Every months during two years
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Every months during two years
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: after two years
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Number of patients alive or died will be measured
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after two years
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Clinical and biological profile of patient with complete molecular remission persistence
Time Frame: after two years
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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.
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after two years
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Treatment costs according to days without imatinib.
Time Frame: after two years
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after two years
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Event-free survival
Time Frame: after two years
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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.
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after two years
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: François-Xavier MAHON, Pr, University Hospital Bordeaux, France
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Imatinib Mesylate
Other Study ID Numbers
- CHUBX 2010/25
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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