Imatinib Response in Patients With Chronic Myeloid Leukemia (CML) in Function of Abl Polymorphisms

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified December 2014 by Centre Hospitalier Universitaire de Nīmes
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier:
NCT01650467
First received: July 24, 2012
Last updated: March 3, 2014
Last verified: December 2014
  Purpose

The main objective of this study is to evaluate the existence of a relationship between the presence of certain abl polymorphisms (or haplotypes) upon CML diagnosis and the occurrence of primary resistance to the treatment of CML by imatinib.


Condition
Leukemia, Myeloid, Chronic-Phase

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Cross-Sectional
Official Title: Imatinib Response in Patients With Chronic Myeloid Leukemia (CML) in Function of Abl Polymorphisms

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Nīmes:

Primary Outcome Measures:
  • abl genotype [ Time Frame: baseline ; at diagnosis ] [ Designated as safety issue: No ]
    The abl genotype will be determined for all subjects


Secondary Outcome Measures:
  • abl genotype [ Time Frame: 12 months after diagnosis ] [ Designated as safety issue: No ]
    The abl genotype will be determined for all subjects

  • bcr-abl leucemic fraction genotype [ Time Frame: 12 months after diagnosis ] [ Designated as safety issue: No ]
    The bcr-able leucemic fraction genotype will be determined for CML patients

  • bcr-abl leucemic fraction genotype [ Time Frame: baseline ; at diagnosis ] [ Designated as safety issue: No ]
    The bcr-able leucemic fraction genotype will be determined for CML patients

  • abl non-leucemic fraction genotype [ Time Frame: baseline ; at diagnosis ] [ Designated as safety issue: No ]
    The abl non-leucemic fraction genotype will be determined for CML patients

  • abl non-leucemic fraction genotype [ Time Frame: 12 months after diagnosis ] [ Designated as safety issue: No ]
    The abl non-leucemic fraction genotype will be determined for CML patients


Biospecimen Retention:   Samples With DNA

Two 7 ml EDTA tubes for genotyping abl and bcr-abl polymorphisms


Estimated Enrollment: 120
Study Start Date: December 2014
Estimated Study Completion Date: June 2017
Estimated Primary Completion Date: June 2017 (Final data collection date for primary outcome measure)
Groups/Cohorts
Healthy controls
60 healthy controls with no hematological pathologies
Imatinib optimal response
30 CML patients who are optimal responders to imatinib treatment
Imatinib primary resistance
30 CML patients who have primary resistance to imatinib treatment

Detailed Description:

The first secondary objective of this study is to identify, in patients not responding to treatment, possible changes in the polymorphisms of interest during the course of the disease, reclassifying such polymorphisms as mutations.

The second secondary objective is to compare the control patients in terms of polymorphism frequency on the nonpathological abl fraction.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population

We will include 60 healthy controls (free of hematologic pathology, seen in genetic counseling) and stratify the recruitment of patients with CML among 30 patients with optimal imatinib response and 30 with primary resistance.

Criteria

Inclusion Criteria:

  • The patient must have given his/her informed and signed consent
  • The patient must be insured or beneficiary of a health insurance plan

Inclusion Criteria for all CML patients

  • Patients diagnosed with CML
  • Treatment with Imatinib in first-line monotherapy and this for at least 12 months
  • RNA and / or cDNA used for diagnosis correctly stored in the biobank

Inclusion Criteria for CML patients already having undergone a follow-up visit at 12 months

  • RNA and / or cDNA used for diagnosis/follow-up correctly stored in the biobank
  • Cytogenetic results are available
  • Absence of ITK mutation for the primary resistance subgroup
  • Validated compliance

Inclusion Criteria for the optimal response group:

  • bcr-abl typing is less than 0.1% at 12 months

Inclusion criteria for the primary resistance group

  • bcr-abl typings is >1% and/or Philadelphia+ is greater than 0

Inclusion Criteria for the control population

  • Absence of hematologic malignancy

Exclusion Criteria:

  • The patient is participating in another study
  • The patient is in an exclusion period determined by a previous study
  • The patient is under judicial protection, under tutorship or curatorship
  • The patient refuses to sign the consent
  • It is impossible to correctly inform the patient
  • The patient is pregnant, parturient, or breastfeeding
  • The patient has a contraindication for a treatment used in this study

Exclusion Criteria for CML patients already having undergone a follow-up visit at 12 months

  • Known or suspected cause for resistance (dose reduced due to intolerance, digestive disease responsible for malabsorption ...)

Exclusion Criteria for the control population

  • History or suspicion of hemopathy
  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: NCT01650467

Contacts
Contact: Jean-Baptiste Gaillard, MD +33.(0)4.66.68.41.60 jean.baptiste.gaillard@chu-nimes.fr
Contact: Carey Suehs, PhD +33.(0)4.66.68.67.88 carey.suehs@chu-nimes.fr

Locations
France
Clinique du Parc Not yet recruiting
Castelnau Le Lez, France, 34170
Sub-Investigator: Carole Exbrayat, MD         
Sub-Investigator: Daniel Donadio, MD         
CHU de Montpellier - Hôpital Saint-Eloi
Montpellier, France, 34295
CHU de Nîmes - Hôpital Universitaire Carémeau Not yet recruiting
Nîmes Cedex 9, France, 30029
Principal Investigator: Jean-Baptiste Gaillard, MD         
Sub-Investigator: Thierry Lavabre-Bertrand, MD, PhD         
Sub-Investigator: Jean Chiesa, MD         
Sub-Investigator: Philippe Khau Van Kien, MD         
Sub-Investigator: Eric Jourdan, MD         
Sub-Investigator: Pascal Bourquard, MD         
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nīmes
Investigators
Principal Investigator: Jean-Baptiste Gaillard, MD Centre Hospitalier Universitaire de Nîmes
  More Information

No publications provided

Responsible Party: Centre Hospitalier Universitaire de Nīmes
ClinicalTrials.gov Identifier: NCT01650467     History of Changes
Other Study ID Numbers: LOCAL/2012/JBG-02, 2012-A00639-34
Study First Received: July 24, 2012
Last Updated: March 3, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
France: Committee for the Protection of Personnes

Keywords provided by Centre Hospitalier Universitaire de Nīmes:
abl polymorphisms

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

ClinicalTrials.gov processed this record on July 29, 2014