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

March 12, 2018 updated by: University Hospital, Bordeaux

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

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Anticipated)

220

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Angers, France, 49033
        • University Hospital Angers
      • Annecy, France
        • CH Annecy
      • Besançon, France
        • CHU Bensançon
      • Bordeaux, France, 33076
        • Institut Bergonie
      • Brest, France, 29285
        • Hôpital Morvan
      • Caen, France
        • CHU Caen
      • Colmar, France, 68000
        • Hôpitaux Civils de Colmar
      • Corbeil-Essonnes, France
        • CH SUd Francilien
      • Creteil, France, 94000
        • Hopital Henri-Mondor
      • Grenoble, France, 38043
        • CHU Grenoble
      • La Roche Sur Yon, France, 85025
        • Centre Hospitalier - La Roche sur Yon
      • Lille, France, 59037
        • Lille University hospital - Hôpital Claude Huriez
      • Limoges, France
        • CHU Dupuytren
      • Lyon, France, 69374
        • Hôpital Edouard HERRIOT
      • Marseille, France, 13273
        • Institut Paoli Calmette
      • Nantes, France, 44035
        • CHU Hôtel-Dieu
      • Nevers, France, 58033
        • Centre Hospitalier de Nevers
      • Nice, France, 06202
        • CHU de Nice - Hôpital Archet 1
      • Paris, France, 75475
        • Hôpital Saint Louis
      • Paris, France, 75743
        • Hôpital Necker-Enfants Malades
      • Pessac, France, 33604
        • University Hospital Bordeaux, Hôpital du Haut Lévêque
      • Poitiers, France, 86021
        • University Hospital Poitiers - Hôpital Jean Bernard
      • Rennes, France, 35033
        • Hôpital Pontchaillou
      • Rouen, France
        • Centre Henri Becquerel
      • Saint Brieuc, France
        • CH Yves Le Foll
      • Saint Pierre, France
        • CH Régional de l'ILE DE LA REUNION/ Groupe Hospitalier Sud
      • Saint-Denis, France, 97405
        • CHR La Réunion
      • Toulouse, France, 31059
        • Hopital Purpan
      • Valence, France
        • CH Valence
      • Vandoeuvre Les Nancy, France, 54500
        • C.H.U. Brabois
      • Vannes, France
        • CH Bretagne Atlantique
      • Versailles, France, 78157
        • Centre Hospitalier de Versailles - Hopital Andre Mignot

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

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
EXPERIMENTAL: Patients
Drug: Imatinib stop
To stop imatinib after inclusion.

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
Every months during two years

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Investigators

  • Principal Investigator: François-Xavier MAHON, Pr, University Hospital Bordeaux, France

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 6, 2011

Primary Completion (ACTUAL)

May 30, 2017

Study Completion (ACTUAL)

May 30, 2017

Study Registration Dates

First Submitted

March 23, 2011

First Submitted That Met QC Criteria

April 26, 2011

First Posted (ESTIMATE)

April 27, 2011

Study Record Updates

Last Update Posted (ACTUAL)

March 13, 2018

Last Update Submitted That Met QC Criteria

March 12, 2018

Last Verified

March 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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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