Clinical trial NCT01343173: Multicenter Trial Estimating the Persistence of Molecular Remission in Chronic Myeloid Leukaemia in Long Term After Stopping Imatinib
Official title: Multicenter Trial Estimating the Persistence of Molecular Remission in Chronic Myeloid Leukaemia in Long Term After Stopping Imatinib
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Myeloid Leukaemia
Keywords: Leukemia
Adult Chronic
Myeloid
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2011-04-27
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Rate of molecular relapse defined by the rate of patients having a significant increasing of BCR-ABL transcript.
timeFrame: Every months during two years
Secondary outcomes:
measure: Overall survival
timeFrame: after two years
measure: Clinical and biological profile of patient with complete molecular remission persistence
timeFrame: after two years
measure: Treatment costs according to days without imatinib.
timeFrame: after two years
measure: Event-free survival
timeFrame: after two years
Other outcomes:
Locations:
city: Angers
country: France
facility: University Hospital Angers
city: Annecy
country: France
facility: CH Annecy
city: Besançon
country: France
facility: CHU Bensançon
city: Bordeaux
country: France
facility: Institut Bergonié
city: Brest
country: France
facility: Hôpital Morvan
city: Caen
country: France
facility: CHU Caen
city: Colmar
country: France
facility: Hôpitaux civils de Colmar
city: Corbeil-Essonnes
country: France
facility: CH Sud Francilien
city: Creteil
country: France
facility: Hôpital Henri-Mondor
city: Grenoble
country: France
facility: CHU Grenoble
city: La Roche Sur Yon
country: France
facility: Centre Hospitalier - La Roche sur Yon
city: Lille
country: France
facility: Lille University hospital - Hôpital Claude Huriez
city: Limoges
country: France
facility: CHU Dupuytren
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Marseille
country: France
facility: Institut Paoli Calmette
city: Nantes
country: France
facility: CHU Hôtel-Dieu
city: Nevers
country: France
facility: Centre Hospitalier de Nevers
city: Nice
country: France
facility: CHU de Nice - Hôpital Archet 1
city: Paris
country: France
facility: Hôpital Saint Louis
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
city: Pessac
country: France
facility: University Hospital Bordeaux, Hôpital du Haut Lévêque
city: Poitiers
country: France
facility: University Hospital Poitiers - Hôpital Jean Bernard
city: Rennes
country: France
facility: Hôpital Pontchaillou
city: Rouen
country: France
facility: Centre Henri Becquerel
city: Saint Brieuc
country: France
facility: CH Yves Le Foll
city: Saint Pierre
country: France
facility: CH Régional de l'ILE DE LA REUNION/ Groupe Hospitalier Sud
city: Saint-Denis
country: France
facility: CHR La Réunion
city: Toulouse
country: France
facility: Hôpital Purpan
city: Valence
country: France
facility: CH Valence
city: Vandoeuvre Les Nancy
country: France
facility: C.H.U. Brabois
city: Vannes
country: France
facility: CH Bretagne Atlantique
city: Versailles
country: France
facility: Centre Hospitalier de Versailles - Hôpital André Mignot
Study officials:
affiliation: University Hospital Bordeaux, France
name: François-Xavier MAHON, Pr
role: PRINCIPAL_INVESTIGATOR
References: