Association Between Side Effects Occurrence and Concentrations of Ibrutinib and Idelalisib

Hematological Malignancies Clinical Trial

— PK-E3I  

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02824159
• Other study ID #: 15 7754 07
• Secondary ID: 2015-005572-17
• Status: Completed
• Start date: April 2016
• Est. completion date: December 2020

Study information

• Verified date: December 2020
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 121
• Est. completion date: December 2020
• Est. primary completion date: November 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Neoplasms

Intervention

Other:
• Blood samples for pharmacokinetics exploration
6 blood sample at regular intervals
• Imagery
Efficacity will be assessed with 3 sessions of resonance magnetic imaging or positron emission tomography scan
• Quality of life scale
Quality of life will be evaluated with questionaries 5 times during the study
• 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)
• 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
• 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 ...)

Locations

Country	Name	City	State
France	Cancer University Institute of Toulouse Oncopole	Toulouse

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Toulouse

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	1 months after treatment initiation
Primary	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	1 months after treatment initiation
Secondary	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)
Secondary	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	1 month after inclusion
Secondary	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	1 month after inclusion
Secondary	The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey		Day 1
Secondary	The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey		3 months after inclusion
Secondary	The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey		6 months after inclusion
Secondary	The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey		12 months after inclusion
Secondary	The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey		18 months after inclusion
Secondary	The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey		24 months after inclusion
Secondary	Response to treatment assessed by positron emission tomography-Scan	complete response, partial, stable disease, disease progression	Day 0
Secondary	Response to treatment assessed by positron emission tomography-Scan	complete response, partial, stable disease, disease progression	6 months after inclusion
Secondary	Response to treatment assessed by positron emission tomography-Scan	complete response, partial, stable disease, disease progression	12 months after inclusion
Secondary	Response to treatment assessed by positron emission tomography-Scan	complete response, partial, stable disease, disease progression	24 months after inclusion
Secondary	Forgetting to take medication reported by the patient as recorded in a logbook given to the patient		3 months after inclusion
Secondary	Forgetting to take medication reported by the patient as recorded in a logbook given to the patient		6 months after inclusion
Secondary	Perception of side effect reported by patient as noted in a logbook by the patient		3 months after inclusion
Secondary	Perception of side effect reported by patient as noted in a logbook by the patient		6 months after inclusion
Secondary	Effect of patients characteristics on plasma balance mean concentration in ibrutinib		1 months after inclusion
Secondary	Effect of patients characteristics on plasma balance mean concentration in idelalisib		1 months after inclusion
Secondary	Effect of patients genetic polymorphism on plasma balance mean concentration in idelalisib		1 months after inclusion
Secondary	Effect of patients therapeutic target DNA polymorphism on treatment response to ibrutinib		Through the completion of study (24 months)
Secondary	Effect of patients therapeutic target DNA polymorphism on treatment response to idelalisib		Through the completion of study (24 months)
Secondary	Treatment failure rate in relation with mean concentration of ibrutinib		1 month after inclusion
Secondary	Treatment failure rate in relation with mean concentration of idelalisib		1 month after inclusion
Secondary	Evaluation of total exposition to ibrutinib (AUCt,ss) with residual concentration at steady state		Through the completion of study (24 months)
Secondary	Evaluation of total exposition to idelalisib (AUCt,ss) with residual concentration at steady state		Through the completion of study (24 months)
Secondary	Association of adverse event and quality of life with Short Form (36) Health Survey		Through the completion of study (24 months)
Secondary	Association of prognostic factors at inclusion and plasma balance mean concentration in ibrutinib		1 month after inclusion
Secondary	Association of prognostic factors at inclusion and plasma balance mean concentration in idelalisib		1 month after inclusion