Association Between Side Effects Occurrence and Concentrations of Ibrutinib and Idelalisib

NCT ID: NCT02824159

Last Updated: 2020-12-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

121 participants

Study Classification

OBSERVATIONAL

Study Start Date

2016-04-30

Study Completion Date

2020-12-31

Brief Summary

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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

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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.

Conditions

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Hematological Malignancies

Keywords

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ibrutinib idelalisib side effect pharmacokinetic plasma balance mean concentration

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Patient with haematologic malignancies

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

Blood samples for pharmacokinetics exploration

Intervention Type OTHER

6 blood sample at regular intervals

Imagery

Intervention Type OTHER

Efficacity will be assessed with 3 sessions of resonance magnetic imaging or positron emission tomography scan

Quality of life scale

Intervention Type OTHER

Quality of life will be evaluated with questionaries 5 times during the study

Detection of adverse events

Intervention Type OTHER

The detection will be assessed using the AMA (assistance des malades ambulatoires) system

Saliva samples

Intervention Type GENETIC

Saliva samples will be collected to explore genetic characteristics of germinal DNA (genes involved in drug pharmacokinetic)

Blood sample

Intervention Type GENETIC

A unique blood sample will be performed in order to determine characteristics of tumoral DNA (resistance to treatment mutation)

Biological statement

Intervention Type OTHER

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

Intervention Type OTHER

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 ...)

Interventions

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Blood samples for pharmacokinetics exploration

6 blood sample at regular intervals

Intervention Type OTHER

Imagery

Efficacity will be assessed with 3 sessions of resonance magnetic imaging or positron emission tomography scan

Intervention Type OTHER

Quality of life scale

Quality of life will be evaluated with questionaries 5 times during the study

Intervention Type OTHER

Detection of adverse events

The detection will be assessed using the AMA (assistance des malades ambulatoires) system

Intervention Type OTHER

Saliva samples

Saliva samples will be collected to explore genetic characteristics of germinal DNA (genes involved in drug pharmacokinetic)

Intervention Type GENETIC

Blood sample

A unique blood sample will be performed in order to determine characteristics of tumoral DNA (resistance to treatment mutation)

Intervention Type GENETIC

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

Intervention Type OTHER

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 ...)

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Toulouse

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Loïc Ysebaert, MD

Role: PRINCIPAL_INVESTIGATOR

Cancer University Institute of Toulouse Oncopole

Locations

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Cancer University Institute of Toulouse Oncopole

Toulouse, , France

Site Status

Countries

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France

References

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Cadot S, Audebert C, Dion C, Ken S, Dupre L, Largeaud L, Laurent C, Ysebaert L, Crauste F, Quillet-Mary A. New pharmacodynamic parameters linked with ibrutinib responses in chronic lymphocytic leukemia: Prospective study in real-world patients and mathematical modeling. PLoS Med. 2024 Jul 22;21(7):e1004430. doi: 10.1371/journal.pmed.1004430. eCollection 2024 Jul.

Reference Type DERIVED
PMID: 39037964 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32328976 (View on PubMed)

Other Identifiers

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2015-005572-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

15 7754 07

Identifier Type: -

Identifier Source: org_study_id