association between side effects occurrence and concentrations of ibrutinib and idelalisib

Conditions: Hematological Malignancies

Summary: recently, european medicines agency approved ibrutinib and idelalisib to treat chronic lymphocytic leukemia (cll) and two lymphomas: follicular lymphoma (fl) for ibrutinib and mantle cell lymphoma (mcl) for idelalisib. clinical trials for ibrutinib and idelalisib were performed with a small number of patients (300-350) and showed several side effects profiles. since, pharmacokinetic properties of these 2 drugs highlight a interindividual variability of pharmacokinetic. the aim of this study is to determine the association between clinically significant side effects occurrence during the first year of treatment and plasma mean concentration of the steady state of ibrutinib or idelalisib at 1 month.

recently, european medicines agency approved ibrutinib and idelalisib in the treatment of chronic lymphocytic leukemia (cll) and two lymphomas: follicular lymphoma (fl) for ibrutinib and mantle cell lymphoma (mcl) for idelalisib. nevertheless, clinical trials for these two drugs were performed for only 300-350 patients and showed several side effects profiles, the most frequent were diarrhea, infection, cutaneous rash... for some patients, treatment had to be reduced or stopped temporary or definitely. pharmacokinetic properties of these two drugs highlight an interindividual pharmacokinetic considerable variability. the aim of this clinical research study is to determine the association between clinically significant side effects occurrence during the first year of treatment (serious adverse reaction and/or grade ctcae ≥ 3 and/or leading a dosage concession) and plasma mean concentration of the steady state of ibrutinib or idelalisib performed at 1 month. to determine plasma mean concentration of the steady state of ibrutinib or idelalisib, blood tests will be performed every scheduled monitoring at visit 1 month during a pharmacokinetic exploration and during scheduled medical consultation (2, 3, 6 and 12 months) and every unscheduled visit in case of side effect occurrence. every scheduled monitoring visit, blood tests will be performed to determine plasma concentration in drug. complementary blood or salivary samples will be collected before the treatment, 24 months later and in case of relapse to determine genetic characteristics. in parallel, a logbook will be completed by the patient to collect side effects. finally, an oncology certified nurse call patients every 2 weeks. in case of side effect occurrence a visit will be organized in the next 3 days and a blood test will be performed.

Eligibility criteria:
inclusion criteria: * evidence of chronic lymphocytic leukaemia (cll), or follicular lymphoma (fl) or mantle cell lymphoma (mcl) and a first prescription of idelalisib or ibrutinib * patients must give written informed consent * patients with health insurance system exclusion criteria: * patient who several blood tests can't be performed (poor venous access) * patients under legal guardian * pregnant or breastfeeding women

Keywords: ibrutinib idelalisib side effect pharmacokinetic plasma balance mean concentration