Distribution of NIlotinib in semen in men treated for chronic Myeloid leukaemiA

Treatment of cancer has developed enormously during the last decade. Especially
for chronic myeloid leukaemia (CML), the advent of TKI*s, such as nilotinib has
dramatically changed prospects of patients with 8 year overall survival rates
increasing from 50% to 90% in approximately 10 years. Many anticancer agents
are known for their reprotoxicity, genotoxicity and mutagenicity. For the TKIs
that are used in CML, teratogenicity is well known when taken by a pregnant
mother. Hypospadias, vertebral-, abdominal wall- and skull abnormalities have
occurred in clearly higher frequencies than the normal background rate.
However, children of men taking TKIs seem not to have an increased risk of
teratogenicity. Whether nilotinib in seminal fluid would pose any risk to the
developing fetus when a pregnant woman has sexual intercourse with a man taking
nilotinib is unknown. During unprotected sexual intercourse the seminal fluid
comes in contact with mucosal tissue of the partner and may be absorbed.
A few studies investigated the risk for women of men on anticancer agents such
as, lenalidomide and thalidomide. Here, detectable amounts of the anti-cancer
drugs in the seminal fluid of men using either lenalidomide or thalidomide
could be demonstrated.
No data is available on nilotinib and the amount present in seminal fluid.
Information is necessary to provide adequate information to male users and
their partners.

This study is designed to determine the level of nilotinib detectable in
seminal fluid of men treated with this tyrosine kinase inhibitor and in order
to form an advise on the use of physical barriers like, condoms, to protect
sexual partners from exposure to nilotinib..

The study is an open-label non-intervention single-centre study. At two
different time points, subjects will collect seminal fluid and blood samples.
The blood samples will be collected by dried blood spots (DBS). This
biosampling method which can be performed at home by the subjects themselves
uses a few drops of blood collected by a finger sting blotted on filter paper
to determine the plasma level of nilotinib.

Chronic myeloid leukaemia requires life-long treatment with nilotinib in most
patients. As at least 25% of patients is below 40 years and life expectancy
seems normal in well responding patients, pregnancy related issues are of major
importance. Currently, use of condoms is advised for any male patient, in order
to protect their sexual partners against nilotinib exposure. If this study
shows very low and acceptable nilotinib levels in seminal fluid, condoms may no
longer be required in cases where contraception is not needed.
The patients burden consists of two extra blood samples by Dried Blood Spot
(DBS) and the effort of collecting and delivery of seminal fluid at two
different time points. Patients may feel embarrassment with participation in
the study.
There are no physiological or physical risk during the study. All patients
receive nilotinib as standard care.