Association Between Side Effects Occurrence and Concentrations of Ibrutinib and Idelalisib

Completed

• Conditions: Hematological Malignancies
• Interventions: Other: Blood samples for pharmacokinetics exploration; Other: Imagery; Other: Quality of life scale; Other: Detection of adverse events; Genetic: Saliva samples; Genetic: Blood sample; Other: Biological statement; Other: Clinical examination

• Registration Number: NCT02824159
• Lead Sponsor: University Hospital, Toulouse

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.

Study Timeline

• Study Start: 2016-04
• Study First Submitted: 2016-06-30
• Study First Submitted QC: 2016-06-30
• Study First Posted: 2016-07-06
• Primary Completion: 2020-11
• Status Verified: 2020-12
• Study Completion: 2020-12
• Last Update Submitted: 2020-12-24
• Last Update Posted: 2020-12-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 121

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patient with haematologic malignancies	Blood samples for pharmacokinetics exploration	Interventions to be administrated are : * Clinical examinations * Biological statement * Blood samples for pharmacokinetics exploration * Imagery with positron emission tomography scan or resonance magnetic imagery * Saliva samples for genetics analyses * Blood samples for treatment mutation resistance search * Quality of life scale questionary * Detection of adverse events
Patient with haematologic malignancies	Imagery	Interventions to be administrated are : * Clinical examinations * Biological statement * Blood samples for pharmacokinetics exploration * Imagery with positron emission tomography scan or resonance magnetic imagery * Saliva samples for genetics analyses * Blood samples for treatment mutation resistance search * Quality of life scale questionary * Detection of adverse events
Patient with haematologic malignancies	Quality of life scale	Interventions to be administrated are : * Clinical examinations * Biological statement * Blood samples for pharmacokinetics exploration * Imagery with positron emission tomography scan or resonance magnetic imagery * Saliva samples for genetics analyses * Blood samples for treatment mutation resistance search * Quality of life scale questionary * Detection of adverse events
Patient with haematologic malignancies	Detection of adverse events	Interventions to be administrated are : * Clinical examinations * Biological statement * Blood samples for pharmacokinetics exploration * Imagery with positron emission tomography scan or resonance magnetic imagery * Saliva samples for genetics analyses * Blood samples for treatment mutation resistance search * Quality of life scale questionary * Detection of adverse events
Patient with haematologic malignancies	Saliva samples	Interventions to be administrated are : * Clinical examinations * Biological statement * Blood samples for pharmacokinetics exploration * Imagery with positron emission tomography scan or resonance magnetic imagery * Saliva samples for genetics analyses * Blood samples for treatment mutation resistance search * Quality of life scale questionary * Detection of adverse events
Patient with haematologic malignancies	Blood sample	Interventions to be administrated are : * Clinical examinations * Biological statement * Blood samples for pharmacokinetics exploration * Imagery with positron emission tomography scan or resonance magnetic imagery * Saliva samples for genetics analyses * Blood samples for treatment mutation resistance search * Quality of life scale questionary * Detection of adverse events
Patient with haematologic malignancies	Biological statement	Interventions to be administrated are : * Clinical examinations * Biological statement * Blood samples for pharmacokinetics exploration * Imagery with positron emission tomography scan or resonance magnetic imagery * Saliva samples for genetics analyses * Blood samples for treatment mutation resistance search * Quality of life scale questionary * Detection of adverse events
Patient with haematologic malignancies	Clinical examination	Interventions to be administrated are : * Clinical examinations * Biological statement * Blood samples for pharmacokinetics exploration * Imagery with positron emission tomography scan or resonance magnetic imagery * Saliva samples for genetics analyses * Blood samples for treatment mutation resistance search * Quality of life scale questionary * Detection of adverse events

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Effect of patients characteristics on plasma balance mean concentration in idelalisib	1 months after inclusion
Effect of patients therapeutic target DNA polymorphism on treatment response to ibrutinib	Through the completion of study (24 months)
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)
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
The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey	24 months after inclusion
Effect of patients characteristics on plasma balance mean concentration in ibrutinib	1 months after inclusion
Response to treatment assessed by positron emission tomography-Scan	24 months after inclusion	complete response, partial, stable disease, disease progression
Effect of patients genetic polymorphism on plasma balance mean concentration in idelalisib	1 months after inclusion
Treatment failure rate in relation with mean concentration of idelalisib	1 month after inclusion
Forgetting to take medication reported by the patient as recorded in a logbook given to the patient	6 months after inclusion
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
Evaluation of total exposition to idelalisib (AUCt,ss) with residual concentration at steady state	Through the completion of study (24 months)
Association of prognostic factors at inclusion and plasma balance mean concentration in idelalisib	1 month after inclusion
Perception of side effect reported by patient as noted in a logbook by the patient	6 months after inclusion
Evaluation of total exposition to ibrutinib (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

Trial Locations

Locations (1)

Cancer University Institute of Toulouse Oncopole; 🇫🇷 Toulouse, France