Impact of the Inhibitors of Tyrosine Kinase on the Male Fertility (GLIFERTI)

March 28, 2011 updated by: Assistance Publique - Hôpitaux de Paris
Evaluate the possible deleterious effects of tyrosine kinase inhibitors on sperm concentration, after 6 months of therapy, which corresponds to 2 cycles of spermatogenesis and on the sperm nuclear integrity. The main comparison criterion will be the mean difference in sperm concentration before and after the 6 month treatment.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Antityrosine - kinases, such as imatinib are presently the gold standard therapy of chronic myeloid leukaemia (CML), with complete cytogenetic responses being achieved in 70-90% of patients receiving the drug as first -line monotherapy. Imatinib selectively inhibits the hybrid oncogen BCR/ABL involved in the genesis of CML and other tyrosine kinases, such as c-kit and platelet derived growth factor receptor (PGDF-R), involved in malignant gastro intestinal stromal tumours (GIST) . Despite its good tolerance, in vivo animal studies have proved that imatinib induces teratogenesis and dose-related effect on spermatogenesis. In humans, few pregnancies involving male CML patients have been reported with one spontaneous abortion, one case of gut malrotation and 15 healthy children. However, in the absence of detailed and definite evidence of the lack of deleterious effect of imatinib on spermatogenesis and sperm nuclear integrity in humans, specific studies are warranted. Male patients (38) will be included in this study if they are 18 to 60 years old, presenting with chronic myeloid leukaemia or malignant GIST and receiving for the first time a treatment by imatinib, a tyrosin-kinase inhibitor, preceded or not by hydroxyurea therapy for less than one month. These patients should have signed the informed consent and be covered by the French social security system. In this open prospective study, each patient will be his own control. The effect of imatinib on the spermatogenesis will be evaluated by the concentration of spermatozoa before the beginning of the treatment and after 6 months of imatinib, representing 2 cycles of spermatogenesis. Patients will be recruited by the onco-haematologists (5 corresponding centres) and referred to the CECOS Tenon. A medical investigator will collect the informed consent and fill the study file. A classical sperm analysis, according to OMS, will be performed. A sample of the ejaculate will be fixed for further analysis of the percentage of sperm nuclei with fragmented DNA (TUNEL procedure). The rest of the semen will be frozen, packaged in straws and stored in liquid nitrogen to be used, if necessary, by the patient if an ART is mandatory to conceive a child.Another sperm recovery will be performed after a period of 6 months under the anti tyrosine-kinase (ATK) therapy and the same sperm analysis will be carried out and the results compared to the first evaluation, before ATK. The plasmatic concentration of imatinib will be determined, for each patient, the day of the second sperm recovery to check the efficiency of ATK administration.

Study Type

Interventional

Enrollment (Actual)

2

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
      • Paris, France, 75012
        • Department of Biology of reproduction (TENON Hospital-APHP)

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 to 60 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Men from 18 to 60 years old
  • Patients recently diagnosed CML or GIST
  • Patients for whom a treatment by an inhibitor of tyrosine kinase in monotherapy is prescribed
  • Patients having signed the informed consent
  • Patients with social security

Exclusion Criteria:

  • Patients already subjected to a treatment potentially sterilizing
  • Patients under supervision or guardianship

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: 1
Patients presenting with chronic myeloid leukaemia or malignant GIST and receiving for the first time a treatment by imatinib, a tyrosin-kinase inhibitor, preceded or not by hydroxyurea therapy for less than one month.
Drug: Imatinib treatment
Imatinib is a tyrosin-kinase inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Average difference of the concentration of spermatozoa in the ejaculate measured before treatment and after 6 months of treatment.
Time Frame: At the inclusion and M6 visits
At the inclusion and M6 visits

Secondary Outcome Measures

Outcome Measure
Time Frame
Analysis of the fragmentation of the spermatic DNA
Time Frame: At the inclusion and M6 visits
At the inclusion and M6 visits
Plasmatic concentration of the inhibitors of tyrosine kinase
Time Frame: At the inclusion and M6 visits
At the inclusion and M6 visits

Collaborators and Investigators

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

Sponsor

Assistance Publique - Hôpitaux de Paris

Investigators

  • Principal Investigator: Jacqueline Mandelbaum, Dr, Assistance Publique - Hopitaux de Paris

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

October 1, 2008

Primary Completion (ACTUAL)

May 1, 2009

Study Completion (ACTUAL)

May 1, 2009

Study Registration Dates

First Submitted

April 29, 2010

First Submitted That Met QC Criteria

April 29, 2010

First Posted (ESTIMATE)

April 30, 2010

Study Record Updates

Last Update Posted (ESTIMATE)

March 29, 2011

Last Update Submitted That Met QC Criteria

March 28, 2011

Last Verified

January 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P070131

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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