NCT02824159

Association Between Side Effects Occurrence and Concentrations of Ibrutinib and Idelalisib

Real Life Assessment of the Association and Its Determinants Between Side Effects and Plasmatic Concentrations of Two Protein Kinase Inhibitors: Ibrutinib (IMBRUVICA®) and Idelalisib (ZYDELIG®) in Hematological Malignancies Treatment.

• Status: Completed
• Phase: —
• Study type: Observational
• Enrollment: 121 (actual)
• Sponsor: University Hospital, Toulouse · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Detailed description

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.

Conditions

• Hematological Malignancies

Interventions

Type	Name	Description
OTHER	Blood samples for pharmacokinetics exploration	6 blood sample at regular intervals
OTHER	Imagery	Efficacity will be assessed with 3 sessions of resonance magnetic imaging or positron emission tomography scan
OTHER	Quality of life scale	Quality of life will be evaluated with questionaries 5 times during the study
OTHER	Detection of adverse events	The detection will be assessed using the AMA (assistance des malades ambulatoires) system
GENETIC	Saliva samples	Saliva samples will be collected to explore genetic characteristics of germinal DNA (genes involved in drug pharmacokinetic)
GENETIC	Blood sample	A unique blood sample will be performed in order to determine characteristics of tumoral DNA (resistance to treatment mutation)
OTHER	Biological statement	The following parameters will be assessed : * Complete blood count * Hemoglobin * Hepatic enzymes * Creatinine clearance * Lactate dehydrogenase rate * Total bilirubin rate * Cluster of differentiation 4 T lymphocytes rate * Total gamma-globulins rate
OTHER	Clinical examination	The clinical examination are composed by : * Weigh, Height and body mass index measurement * Clinical state of patient during examination * Stage of the disease (OMS grade, binet classification, Ahn Arbor classification) * Presence of B symptomatology * Prognostic factors (Genetic, Mantle Cell Lymphoma International Prognostic Index, Follicular Lymphoma International Prognostic Index, presence of lymph nodes, other target organs ...)

Timeline

• Start date: 2016-04-01
• Primary completion: 2020-11-01
• Completion: 2020-12-01
• First posted: 2016-07-06
• Last updated: 2020-12-28

Locations

1 site across 1 country: France