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

Chronic Myeloid Leukaemia Clinical Trial

— STIM 2  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01343173
• Other study ID #: CHUBX 2010/25
• Status: Completed
• Phase: N/A
• First received: March 23, 2011
• Last updated: March 12, 2018
• Start date: April 6, 2011
• Est. completion date: May 30, 2017

Study information

• Verified date: March 2018
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 220
• Est. completion date: May 30, 2017
• Est. primary completion date: May 30, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

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

Intervention

Drug:
• Imatinib stop
To stop imatinib after inclusion.

Locations

Country	Name	City	State
France	University Hospital Angers	Angers
France	CH Annecy	Annecy
France	CHU Bensançon	Besançon
France	Institut Bergonié	Bordeaux
France	Hôpital Morvan	Brest
France	CHU Caen	Caen
France	Hôpitaux civils de Colmar	Colmar
France	CH Sud Francilien	Corbeil-Essonnes
France	Hôpital Henri-Mondor	Creteil
France	CHU Grenoble	Grenoble
France	Centre Hospitalier - La Roche sur Yon	La Roche Sur Yon
France	Lille University hospital - Hôpital Claude Huriez	Lille
France	CHU Dupuytren	Limoges
France	Hôpital Edouard Herriot	Lyon
France	Institut Paoli Calmette	Marseille
France	CHU Hôtel-Dieu	Nantes
France	Centre Hospitalier de Nevers	Nevers
France	CHU de Nice - Hôpital Archet 1	Nice
France	Hôpital Necker-Enfants Malades	Paris
France	Hôpital Saint Louis	Paris
France	University Hospital Bordeaux, Hôpital du Haut Lévêque	Pessac
France	University Hospital Poitiers - Hôpital Jean Bernard	Poitiers
France	Hôpital Pontchaillou	Rennes
France	Centre Henri Becquerel	Rouen
France	CH Yves Le Foll	Saint Brieuc
France	CH Régional de l'ILE DE LA REUNION/ Groupe Hospitalier Sud	Saint Pierre
France	CHR La Réunion	Saint-Denis
France	Hôpital Purpan	Toulouse
France	CH Valence	Valence
France	C.H.U. Brabois	Vandoeuvre Les Nancy
France	CH Bretagne Atlantique	Vannes
France	Centre Hospitalier de Versailles - Hôpital André Mignot	Versailles

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of molecular relapse defined by the rate of patients having a significant increasing of BCR-ABL transcript.		Every months during two years
Secondary	Overall survival	Number of patients alive or died will be measured	after two years
Secondary	Clinical and biological profile of patient with complete molecular remission persistence	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.	after two years
Secondary	Treatment costs according to days without imatinib.		after two years
Secondary	Event-free survival	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.	after two years