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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by University Hospital, Bordeaux
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT01343173
First received: March 23, 2011
Last updated: October 29, 2014
Last verified: October 2014
  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

Contacts
Contact: François-Xavier MAHON, Pr Francois-Xavier.Mahon@u-bordeaux2.fr

Locations
France
University Hospital Angers Recruiting
Angers, France, 49033
Contact: Martine GARDEMBAS-PAIN, Dr         
Principal Investigator: Martine GARDEMBAS-PAIN, Dr         
CH Annecy Recruiting
Annecy, France
Principal Investigator: Pascale CONY-MAKHOUL, Dr         
CHU Bensançon Recruiting
Besançon, France
Contact: Fabrice LAROSA, Dr         
Principal Investigator: Fabrice LAROSA, Dr         
Institut Bergonié Recruiting
Bordeaux, France, 33076
Contact: Gabriel ETIENNE, Pr         
Principal Investigator: Gabriel ETIENNE, Dr         
Hôpital Morvan Recruiting
Brest, France, 29285
Contact: Jean-Christophe IANOTTO, Dr         
Principal Investigator: Jean-Christophe IANOTTO, Dr         
CHU Caen Recruiting
Caen, France
Contact: Hyacinthe JOHNSON-ANSAH, Dr         
Principal Investigator: Hyacinthe JOHNSON-ANSAH, Dr         
Hôpitaux civils de Colmar Not yet recruiting
Colmar, France, 68000
Contact: Catherine HUMBRECHT-KRAUT, Dr         
Principal Investigator: Catherine HUMBRECHT-KRAUT, Dr         
JOLY Recruiting
Corbeil-Essones, France
Contact: Bertrand JOLY, Dr         
Principal Investigator: Bertrand JOLY, Dr         
Hôpital Henri-Mondor Recruiting
Creteil, France, 94000
Contact: Michel TULLIEZ, Pr         
Principal Investigator: Michel TULLIEZ, Pr         
CHU Grenoble Recruiting
Grenoble, France, 38043
Contact: Jean-Yves CAHN, Pr.         
Principal Investigator: Jean-Yves CAHN, Pr         
Centre hospitalier - La roche sur yon Recruiting
La Roche Sur Yon, France, 85025
Contact: Bruno VILLEMAGNE, Dr         
Principal Investigator: Bruno VILLEMAGNE, Dr         
Lille University hospital - Hôpital Claude Huriez Recruiting
Lille, France, 59037
Contact: Marie Pierre Noel, Pr         
Principal Investigator: Marie-Pierre NOEL, Dr         
Hôpital Edouard Herriot Recruiting
Lyon, France, 69374
Contact: NICOLINI Franck, Pr         
Principal Investigator: Franck NICOLINI, Dr         
Institut Paoli Calmette Recruiting
Marseille, France, 13273
Contact: Aude CHARBONNIER, Dr         
Principal Investigator: Aude CHARBONNIER, Dr         
CHU Hôtel-Dieu Recruiting
Nantes, France, 44035
Contact: Viviane DUBRUILLE, Dr         
Principal Investigator: Viviane DUBRUILLE, Dr         
Centre Hospitalier de Nevers Recruiting
Nevers, France, 58033
Contact: Isabelle ROCHE-LACHAISE, Dr         
Principal Investigator: Isabelle ROCHE-LACHAISE, Dr         
CHU de Nice - Hôpital Archet 1 Recruiting
Nice, France, 06202
Contact: Laurence LEGROS, Dr         
Principal Investigator: Laurence LEGROS, Dr         
Hôpital Necker-Enfants Malades Recruiting
Paris, France, 75743
Contact: Isabelle Desmoulins-Louvrier, Dr         
Principal Investigator: Bruno VARET, Pr         
Hôpital Saint Louis Recruiting
Paris, France, 75475
Principal Investigator: Philippe ROUSSELOT, Dr         
University Hospital Bordeaux, Hôpital du Haut Lévêque Recruiting
Pessac, France, 33604
Contact: François-Xavier MAHON, Pr       Francois-Xavier.Mahon@u-bordeaux2.fr   
Principal Investigator: François-Xavier MAHON, Pr         
Sub-Investigator: Gérald MARIT, Pr         
University Hospital Poitiers - Hôpital Jean Bernard Recruiting
Poitiers, France, 86021
Contact: François GUILHOT, Pr         
Principal Investigator: François GUILHOT, Pr         
Sub-Investigator: Lydia ROY, Dr         
Sub-Investigator: Pierre-Jean Saulnier, Dr.         
Hôpital Pontchaillou Recruiting
Rennes, France, 35033
Contact: Martine Escoffre-Barbe, Dr         
Principal Investigator: Martine Escoffre-Barbe, Dr         
Centre Henri Becquerel Recruiting
Rouen, France
Contact: Pascal LENAIN, Dr         
Principal Investigator: Pascal LENAIN, Dr         
CH Régional de l'ILE DE LA REUNION/ Groupe Hospitalier Sud Recruiting
Saint Pierre, France
Contact: Patrica ZUNIC, Dr         
Principal Investigator: Patricia ZUNIC, Dr         
CHR La Réunion Recruiting
Saint-Denis, France, 97405
Contact: Philippe AGAPE, Pr         
Principal Investigator: Philippe AGAPE, Pr         
Hôpital Purpan Recruiting
Toulouse, France, 31059
Principal Investigator: Françoise RIGAL-HUGUET, Dr         
CH Valence Recruiting
Valence, France
Contact: Jixing LIU, Dr         
Principal Investigator: Jixing LIU, Dr         
C.H.U. Brabois Recruiting
Vandoeuvre Les Nancy, France, 54500
Contact: Agnès-Paule GUERCI, Dr         
Principal Investigator: Agnès-Paule GUERCI, Dr         
Centre Hospitalier de Versailles - Hôpital André Mignot Recruiting
Versailles, France, 78157
Contact: Philippe ROUSSELOT, Dr         
Principal Investigator: Philippe ROUSSELOT, Pr         
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: October 29, 2014
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 November 24, 2014