A Pilot Study on Intermittent Ibrutinib in Patients With Advanced-phase Chronic Lymphocytic Leukemia (CLL)
Status:
Recruiting
Trial end date:
2027-12-01
Target enrollment:
Participant gender:
Summary
Ibrutinib, an inhibitor of Bruton´s tyrosine kinase (BTK) is approved in CLL as continuous,
daily administration of 420 mg orally until progression. Ibrutinib drug costs in health care
are rapidly increasing and are difficult to predict, as long-term follow up analyses have
shown that many patients remain on therapy for several years, in some cases even many years.
It has been observed that patients who stop ibrutinib due to side effects may often remain
with continued CLL disease control i.e. in stable partial remission even when off ibrutinib
therapy. There are also emerging data on mutations within BTK, with loss of efficacy of
ibrutinib, during long-term continuous administration. These observations raise the question
whether alternative dosing strategies may be feasible. This pilot study will explore
intermittent and repeated dosing of ibrutinib, until alternative therapy is required due to
resistance or intolerance to ibrutinib. An "ON-OFF" dosing strategy will be applied, where
advanced-phase CLL patients who have received at least 6 months of ibrutinib and who have
achieved a stable PR will stop ibrutinib and be followed off therapy until clinical
progression, at which ibrutinib will be re-instituted. Such "ON-OFF" ibrutinib cycles may be
repeated until non-tolerability or resistance, or need of continuous dosing of ibrutinib
(i.e. early progression when off the drug). If successful, the study will indicate a way
forward towards reducing ibrutinib drug costs in health care without affecting long-term
disease control, possibly also with fewer ibrutinib-related side effects due to a lower
cumulative dose of ibrutinib. Long-term effects on potential mutations within BTK and its
downstream signaling molecules will also be analysed.