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

This study has been completed.
Sponsor:
Information provided by:
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01114087
First received: April 29, 2010
Last updated: March 28, 2011
Last verified: January 2011
  Purpose

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.


Condition Intervention
Chronic Myeloid Leukemia
Gastrointestinal Stromal Tumors
Drug: Imatinib treatment

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Impact of the Inhibitors of Tyrosine Kinase on the Male Fertility

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Analysis of the fragmentation of the spermatic DNA [ Time Frame: At the inclusion and M6 visits ] [ Designated as safety issue: No ]
  • Plasmatic concentration of the inhibitors of tyrosine kinase [ Time Frame: At the inclusion and M6 visits ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: October 2008
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: Imatinib 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.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01114087

Locations
France
Department of Biology of reproduction (TENON Hospital-APHP)
Paris, France, 75012
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Jacqueline Mandelbaum, Dr Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Amel Ouslimani, Department Clinical Reseach of Developpement
ClinicalTrials.gov Identifier: NCT01114087     History of Changes
Other Study ID Numbers: P070131
Study First Received: April 29, 2010
Last Updated: March 28, 2011
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
Spermatogenesis
Inhibitors of tyrosine kinase
Fragmentation of the spermatic DNA

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

ClinicalTrials.gov processed this record on September 16, 2014