Impact of the Inhibitors of Tyrosine Kinase on the Male Fertility
Condition: Chronic Myeloid Leukemia; Gastrointestinal Stromal Tumors
MeSH terms: Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Gastrointestinal Stromal Tumors
Study type: Interventional

Summary: 
      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.
    

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.
    

Intervention name(s): Imatinib treatment
Intervention type(s): Drug
Intervention description(s): Imatinib is a tyrosin-kinase inhibitor
Intervention MeSH terms: Imatinib Mesylate
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Spermatogenesis; Inhibitors of tyrosine kinase; Fragmentation of the spermatic DNA