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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT01343173
First received: March 23, 2011
Last updated: July 22, 2015
Last verified: July 2015
  Purpose

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 Intervention
Chronic Myeloid Leukaemia
Drug: Imatinib stop

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Time Frame: after two years ] [ Designated as safety issue: No ]
    Number of patients alive or died will be measured

  • Clinical and biological profile of patient with complete molecular remission persistence [ Time Frame: after two years ] [ Designated as safety issue: No ]
    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. [ Time Frame: after two years ] [ Designated as safety issue: No ]
  • Event-free survival [ Time Frame: after two years ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 220
Study Start Date: April 2011
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: July 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Patients Drug: Imatinib stop
To stop imatinib after inclusion.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01343173

Locations
France
University Hospital Angers
Angers, France, 49033
CH Annecy
Annecy, France
CHU Bensançon
Besançon, France
Institut Bergonié
Bordeaux, France, 33076
Hôpital Morvan
Brest, France, 29285
CHU Caen
Caen, France
Hôpitaux civils de Colmar
Colmar, France, 68000
CH Sud Francilien
Corbeil-Essones, France
Hôpital Henri-Mondor
Creteil, France, 94000
CHU Grenoble
Grenoble, France, 38043
Centre Hospitalier - La Roche sur Yon
La Roche Sur Yon, France, 85025
Lille University hospital - Hôpital Claude Huriez
Lille, France, 59037
CHU Dupuytren
Limoges, France
Hôpital Edouard Herriot
Lyon, France, 69374
Institut Paoli Calmette
Marseille, France, 13273
CHU Hôtel-Dieu
Nantes, France, 44035
Centre Hospitalier de Nevers
Nevers, France, 58033
CHU de Nice - Hôpital Archet 1
Nice, France, 06202
Hôpital Necker-Enfants Malades
Paris, France, 75743
Hôpital Saint Louis
Paris, France, 75475
University Hospital Bordeaux, Hôpital du Haut Lévêque
Pessac, France, 33604
University Hospital Poitiers - Hôpital Jean Bernard
Poitiers, France, 86021
Hôpital Pontchaillou
Rennes, France, 35033
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, 97405
Hôpital Purpan
Toulouse, France, 31059
CH Valence
Valence, France
C.H.U. Brabois
Vandoeuvre Les Nancy, France, 54500
CH Bretagne Atlantique
Vannes, France
Centre Hospitalier de Versailles - Hôpital André Mignot
Versailles, France, 78157
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
Principal Investigator: François-Xavier MAHON, Pr University Hospital Bordeaux, France
  More Information

No publications provided

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT01343173     History of Changes
Other Study ID Numbers: CHUBX 2010/25
Study First Received: March 23, 2011
Last Updated: July 22, 2015
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
Leukemia
Adult Chronic
Myeloid

Additional relevant MeSH terms:
Leukemia
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Imatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on August 27, 2015