Clinical trial NCT02824159: Association Between Side Effects Occurrence and Concentrations of Ibrutinib and Idelalisib
Official title: 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.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hematological Malignancies
Keywords: ibrutinib
idelalisib
side effect
pharmacokinetic
plasma balance mean concentration
Lead sponsor: University Hospital, Toulouse
Sponsor class: OTHER
First posted: 2016-07-06
Enrollment: 121
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with haematologic malignancies

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.

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

Primary outcomes:
measure: Evaluation of clinically significant side effect occurence with plasma balance mean concentration in ibrutinib
timeFrame: 1 months after treatment initiation
measure: Evaluation of clinically significant side effect occurence with plasma balance mean concentration in idelalisib
timeFrame: 1 months after treatment initiation
Secondary outcomes:
measure: 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
timeFrame: through the end of study (24 months)
measure: Plasma balance mean concentration in ibrutinib with collection of blood samples
timeFrame: 1 month after inclusion
measure: Plasma balance mean concentration in idelalisib with collection of blood samples
timeFrame: 1 month after inclusion
measure: The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey
timeFrame: Day 1
measure: The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey
timeFrame: 3 months after inclusion
measure: The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey
timeFrame: 6 months after inclusion
measure: The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey
timeFrame: 12 months after inclusion
measure: The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey
timeFrame: 18 months after inclusion
measure: The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey
timeFrame: 24 months after inclusion
measure: Response to treatment assessed by positron emission tomography-Scan
timeFrame: Day 0
measure: Response to treatment assessed by positron emission tomography-Scan
timeFrame: 6 months after inclusion
measure: Response to treatment assessed by positron emission tomography-Scan
timeFrame: 12 months after inclusion
measure: Response to treatment assessed by positron emission tomography-Scan
timeFrame: 24 months after inclusion
measure: Forgetting to take medication reported by the patient as recorded in a logbook given to the patient
timeFrame: 3 months after inclusion
measure: Forgetting to take medication reported by the patient as recorded in a logbook given to the patient
timeFrame: 6 months after inclusion
measure: Perception of side effect reported by patient as noted in a logbook by the patient
timeFrame: 3 months after inclusion
measure: Perception of side effect reported by patient as noted in a logbook by the patient
timeFrame: 6 months after inclusion
measure: Effect of patients characteristics on plasma balance mean concentration in ibrutinib
timeFrame: 1 months after inclusion
measure: Effect of patients characteristics on plasma balance mean concentration in idelalisib
timeFrame: 1 months after inclusion
measure: Effect of patients genetic polymorphism on plasma balance mean concentration in idelalisib
timeFrame: 1 months after inclusion
measure: Effect of patients therapeutic target DNA polymorphism on treatment response to ibrutinib
timeFrame: Through the completion of study (24 months)
measure: Effect of patients therapeutic target DNA polymorphism on treatment response to idelalisib
timeFrame: Through the completion of study (24 months)
measure: Treatment failure rate in relation with mean concentration of ibrutinib
timeFrame: 1 month after inclusion
measure: Treatment failure rate in relation with mean concentration of idelalisib
timeFrame: 1 month after inclusion
measure: Evaluation of total exposition to ibrutinib (AUCt,ss) with residual concentration at steady state
timeFrame: Through the completion of study (24 months)
measure: Evaluation of total exposition to idelalisib (AUCt,ss) with residual concentration at steady state
timeFrame: Through the completion of study (24 months)
measure: Association of adverse event and quality of life with Short Form (36) Health Survey
timeFrame: Through the completion of study (24 months)
measure: Association of prognostic factors at inclusion and plasma balance mean concentration in ibrutinib
timeFrame: 1 month after inclusion
measure: Association of prognostic factors at inclusion and plasma balance mean concentration in idelalisib
timeFrame: 1 month after inclusion
Other outcomes:
Locations:
city: Toulouse
country: France
facility: Cancer University Institute of Toulouse Oncopole
Study officials:
affiliation: Cancer University Institute of Toulouse Oncopole
name: Loïc Ysebaert, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gallais F, Ysebaert L, Despas F, De Barros S, Dupre L, Quillet-Mary A, Protin C, Thomas F, Oberic L, Allal B, Chatelut E, White-Koning M. Population Pharmacokinetics of Ibrutinib and Its Dihydrodiol Metabolite in Patients with Lymphoid Malignancies. Clin Pharmacokinet. 2020 Sep;59(9):1171-1183. doi: 10.1007/s40262-020-00884-0.