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.
Study Type
OBSERVATIONAL
Enrollment
121
6 blood sample at regular intervals
Efficacity will be assessed with 3 sessions of resonance magnetic imaging or positron emission tomography scan
Quality of life will be evaluated with questionaries 5 times during the study
The detection will be assessed using the AMA (assistance des malades ambulatoires) system
Saliva samples will be collected to explore genetic characteristics of germinal DNA (genes involved in drug pharmacokinetic)
A unique blood sample will be performed in order to determine characteristics of tumoral DNA (resistance to treatment mutation)
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
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 ...)
Cancer University Institute of Toulouse Oncopole
Toulouse, France
Evaluation of clinically significant side effect occurence with plasma balance mean concentration in ibrutinib
Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit
Time frame: 1 months after treatment initiation
Evaluation of clinically significant side effect occurence with plasma balance mean concentration in idelalisib
Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit
Time frame: 1 months after treatment initiation
Clinically significant side effect occurrence (Serious adverse reaction and/or grade CTCAE ≥ 3 and/or leading a dosage concession) as assessed by AMA (Assistance des Malades Ambulatoires) system
Time frame: through the end of study (24 months)
Plasma balance mean concentration in ibrutinib with collection of blood samples
Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit
Time frame: 1 month after inclusion
Plasma balance mean concentration in idelalisib with collection of blood samples
Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit
Time frame: 1 month after inclusion
The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey
Time frame: Day 1
The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey
Time frame: 3 months after inclusion
The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey
Time frame: 6 months after inclusion
The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey
Time frame: 12 months after inclusion
The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey
Time frame: 18 months after inclusion
The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey
Time frame: 24 months after inclusion
Response to treatment assessed by positron emission tomography-Scan
complete response, partial, stable disease, disease progression
Time frame: Day 0
Response to treatment assessed by positron emission tomography-Scan
complete response, partial, stable disease, disease progression
Time frame: 6 months after inclusion
Response to treatment assessed by positron emission tomography-Scan
complete response, partial, stable disease, disease progression
Time frame: 12 months after inclusion
Response to treatment assessed by positron emission tomography-Scan
complete response, partial, stable disease, disease progression
Time frame: 24 months after inclusion
Forgetting to take medication reported by the patient as recorded in a logbook given to the patient
Time frame: 3 months after inclusion
Forgetting to take medication reported by the patient as recorded in a logbook given to the patient
Time frame: 6 months after inclusion
Perception of side effect reported by patient as noted in a logbook by the patient
Time frame: 3 months after inclusion
Perception of side effect reported by patient as noted in a logbook by the patient
Time frame: 6 months after inclusion
Effect of patients characteristics on plasma balance mean concentration in ibrutinib
Time frame: 1 months after inclusion
Effect of patients characteristics on plasma balance mean concentration in idelalisib
Time frame: 1 months after inclusion
Effect of patients genetic polymorphism on plasma balance mean concentration in idelalisib
Time frame: 1 months after inclusion
Effect of patients therapeutic target DNA polymorphism on treatment response to ibrutinib
Time frame: Through the completion of study (24 months)
Effect of patients therapeutic target DNA polymorphism on treatment response to idelalisib
Time frame: Through the completion of study (24 months)
Treatment failure rate in relation with mean concentration of ibrutinib
Time frame: 1 month after inclusion
Treatment failure rate in relation with mean concentration of idelalisib
Time frame: 1 month after inclusion
Evaluation of total exposition to ibrutinib (AUCt,ss) with residual concentration at steady state
Time frame: Through the completion of study (24 months)
Evaluation of total exposition to idelalisib (AUCt,ss) with residual concentration at steady state
Time frame: Through the completion of study (24 months)
Association of adverse event and quality of life with Short Form (36) Health Survey
Time frame: Through the completion of study (24 months)
Association of prognostic factors at inclusion and plasma balance mean concentration in ibrutinib
Time frame: 1 month after inclusion
Association of prognostic factors at inclusion and plasma balance mean concentration in idelalisib
Time frame: 1 month after inclusion
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