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

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.

Study Overview

• Status: Withdrawn
• Conditions: Leukemia, Myeloid, Chronic-Phase

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.

• Study Type: Observational

Contacts and Locations

Study Locations

• France
  • Castelnau Le Lez, France, 34170
    • Clinique du parc
  • Montpellier, France, 34295
    • CHU de Montpellier - Hôpital Saint-Eloi
  • Nîmes Cedex 9, France, 30029
    • CHU de Nimes - Hopital Universitaire Caremeau

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
abl genotype	The abl genotype will be determined for all subjects	baseline ; at diagnosis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
abl genotype	The abl genotype will be determined for all subjects	12 months after diagnosis
bcr-abl leucemic fraction genotype	The bcr-able leucemic fraction genotype will be determined for CML patients	12 months after diagnosis
bcr-abl leucemic fraction genotype	The bcr-able leucemic fraction genotype will be determined for CML patients	baseline ; at diagnosis
abl non-leucemic fraction genotype	The abl non-leucemic fraction genotype will be determined for CML patients	baseline ; at diagnosis
abl non-leucemic fraction genotype	The abl non-leucemic fraction genotype will be determined for CML patients	12 months after diagnosis

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire de Nīmes
• Investigators: Principal Investigator: Jean-Baptiste Gaillard, MD, Centre Hospitalier Universitaire de Nîmes

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): June 1, 2017

Study Registration Dates

• First Submitted: July 24, 2012
• First Submitted That Met QC Criteria: July 24, 2012
• First Posted (Estimate): July 26, 2012

Study Record Updates

• Last Update Posted (Estimate): February 1, 2017
• Last Update Submitted That Met QC Criteria: January 31, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: abl polymorphisms
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myeloproliferative Disorders; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Chronic-Phase
• Other Study ID Numbers: LOCAL/2012/JBG-02; 2012-A00639-34 (Other Identifier: RCB number)