STIM 2: Multicenter Trial Estimating the Persistence of Molecular Remission in Chronic Myeloid Leukaemia in Long Term After Stopping Imatinib

Sponsor

University Hospital, Bordeaux (Other)

Overall Status

Completed

CT.gov ID

NCT01343173

Collaborator

(none)

220

Enrollment

Locations

Arm

73.8

Actual Duration (Months)

6.9

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myeloid Leukaemia	Drug: Imatinib stop	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

220 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 6, 2011

Actual Primary Completion Date :

May 30, 2017

Actual Study Completion Date :

May 30, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Patients	Drug: Imatinib stop To stop imatinib after inclusion.

Arm

Intervention/Treatment

Experimental: Patients

Drug: Imatinib stop

To stop imatinib after inclusion.

Outcome Measures

Primary Outcome Measures

Rate of molecular relapse defined by the rate of patients having a significant increasing of BCR-ABL transcript. [Every months during two years]

Secondary Outcome Measures

Overall survival [after two years]
Number of patients alive or died will be measured
Clinical and biological profile of patient with complete molecular remission persistence [after two years]
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.
Treatment costs according to days without imatinib. [after two years]
Event-free survival [after two years]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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).

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	University Hospital Angers	Angers	France	49033
2	CH Annecy	Annecy	France
3	CHU Bensançon	Besançon	France
4	Institut Bergonié	Bordeaux	France	33076
5	Hôpital Morvan	Brest	France	29285
6	CHU Caen	Caen	France
7	Hôpitaux civils de Colmar	Colmar	France	68000
8	CH Sud Francilien	Corbeil-Essonnes	France
9	Hôpital Henri-Mondor	Creteil	France	94000
10	CHU Grenoble	Grenoble	France	38043
11	Centre Hospitalier - La Roche sur Yon	La Roche Sur Yon	France	85025
12	Lille University hospital - Hôpital Claude Huriez	Lille	France	59037
13	CHU Dupuytren	Limoges	France
14	Hôpital Edouard Herriot	Lyon	France	69374
15	Institut Paoli Calmette	Marseille	France	13273
16	CHU Hôtel-Dieu	Nantes	France	44035
17	Centre Hospitalier de Nevers	Nevers	France	58033
18	CHU de Nice - Hôpital Archet 1	Nice	France	06202
19	Hôpital Saint Louis	Paris	France	75475
20	Hôpital Necker-Enfants Malades	Paris	France	75743
21	University Hospital Bordeaux, Hôpital du Haut Lévêque	Pessac	France	33604
22	University Hospital Poitiers - Hôpital Jean Bernard	Poitiers	France	86021
23	Hôpital Pontchaillou	Rennes	France	35033
24	Centre Henri Becquerel	Rouen	France
25	CH Yves Le Foll	Saint Brieuc	France
26	CH Régional de l'ILE DE LA REUNION/ Groupe Hospitalier Sud	Saint Pierre	France
27	CHR La Réunion	Saint-Denis	France	97405
28	Hôpital Purpan	Toulouse	France	31059
29	CH Valence	Valence	France
30	C.H.U. Brabois	Vandoeuvre Les Nancy	France	54500
31	CH Bretagne Atlantique	Vannes	France
32	Centre Hospitalier de Versailles - Hôpital André Mignot	Versailles	France	78157