Hematological Malignancies
Conditions
Keywords
ibrutinib, idelalisib, side effect, pharmacokinetic, plasma balance mean concentration
Brief 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.
Interventions
OTHERBlood samples for pharmacokinetics exploration
6 blood sample at regular intervals
OTHERImagery
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
OTHERDetection of adverse events
The detection will be assessed using the AMA (assistance des malades ambulatoires) system
GENETICSaliva samples
Saliva samples will be collected to explore genetic characteristics of germinal DNA (genes involved in drug pharmacokinetic)
GENETICBlood sample
A unique blood sample will be performed in order to determine characteristics of tumoral DNA (resistance to treatment mutation)
OTHERBiological 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
OTHERClinical 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 ...)
Sponsors
University Hospital, Toulouse
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation of clinically significant side effect occurence with plasma balance mean concentration in ibrutinib | 1 months after treatment initiation | Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit |
| Evaluation of clinically significant side effect occurence with plasma balance mean concentration in idelalisib | 1 months after treatment initiation | Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Plasma balance mean concentration in idelalisib with collection of blood samples | 1 month after inclusion | Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit |
| The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey | Day 1 | — |
| Response to treatment assessed by positron emission tomography-Scan | Day 0 | complete response, partial, stable disease, disease progression |
| Forgetting to take medication reported by the patient as recorded in a logbook given to the patient | 3 months after inclusion | — |
| Perception of side effect reported by patient as noted in a logbook by the patient | 3 months after inclusion | — |
| Effect of patients characteristics on plasma balance mean concentration in ibrutinib | 1 months after inclusion | — |
| Effect of patients characteristics on plasma balance mean concentration in idelalisib | 1 months after inclusion | — |
| Effect of patients genetic polymorphism on plasma balance mean concentration in idelalisib | 1 months after inclusion | — |
| 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 | through the end of study (24 months) | — |
| Effect of patients therapeutic target DNA polymorphism on treatment response to idelalisib | Through the completion of study (24 months) | — |
| Treatment failure rate in relation with mean concentration of ibrutinib | 1 month after inclusion | — |
| Treatment failure rate in relation with mean concentration of idelalisib | 1 month after inclusion | — |
| Evaluation of total exposition to ibrutinib (AUCt,ss) with residual concentration at steady state | Through the completion of study (24 months) | — |
| Evaluation of total exposition to idelalisib (AUCt,ss) with residual concentration at steady state | Through the completion of study (24 months) | — |
| Association of adverse event and quality of life with Short Form (36) Health Survey | Through the completion of study (24 months) | — |
| Association of prognostic factors at inclusion and plasma balance mean concentration in ibrutinib | 1 month after inclusion | — |
| Association of prognostic factors at inclusion and plasma balance mean concentration in idelalisib | 1 month after inclusion | — |
| Effect of patients therapeutic target DNA polymorphism on treatment response to ibrutinib | Through the completion of study (24 months) | — |
| Plasma balance mean concentration in ibrutinib with collection of blood samples | 1 month after inclusion | Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit |
Countries
France
Outcome results
None listed