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Completed

NCT Number: NCT02824159

Association Between Side Effects Occurrence and Concentrations of Ibrutinib and Idelalisib

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.

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Key information

Conditions

Hematological Malignancies Hematologic Diseases Hematologic Neoplasms Hemic and Lymphatic Diseases Neoplasms Neoplasms by Site

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

Cancer University Institute of Toulouse Oncopole

Toulouse, 31059, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Blood samples for pharmacokinetics exploration

Other

6 blood sample at regular intervals

Imagery

Other

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

Quality of life scale

Other

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

Detection of adverse events

Other

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

Saliva samples

Genetic

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

blood sample

Genetic

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

Biological statement

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

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 ...)

Primary outcomes

  1. Evaluation of clinically significant side effect occurence with plasma balance mean concentration in ibrutinib

    Time frame: 1 months after treatment initiation

    Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit

  2. Evaluation of clinically significant side effect occurence with plasma balance mean concentration in idelalisib

    Time frame: 1 months after treatment initiation

    Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit

Secondary outcomes

  1. 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

    Time frame: through the end of study (24 months)

  2. Plasma balance mean concentration in ibrutinib with collection of blood samples

    Time frame: 1 month after inclusion

    Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit

  3. Plasma balance mean concentration in idelalisib with collection of blood samples

    Time frame: 1 month after inclusion

    Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit

  4. The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey

    Time frame: Day 1

  5. The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey

    Time frame: 3 months after inclusion

  6. The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey

    Time frame: 6 months after inclusion

  7. The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey

    Time frame: 12 months after inclusion

  8. The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey

    Time frame: 18 months after inclusion

  9. The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey

    Time frame: 24 months after inclusion

  10. Response to treatment assessed by positron emission tomography-Scan

    Time frame: Day 0

    complete response, partial, stable disease, disease progression

  11. Response to treatment assessed by positron emission tomography-Scan

    Time frame: 6 months after inclusion

    complete response, partial, stable disease, disease progression

  12. Response to treatment assessed by positron emission tomography-Scan

    Time frame: 12 months after inclusion

    complete response, partial, stable disease, disease progression

  13. Response to treatment assessed by positron emission tomography-Scan

    Time frame: 24 months after inclusion

    complete response, partial, stable disease, disease progression

  14. Forgetting to take medication reported by the patient as recorded in a logbook given to the patient

    Time frame: 3 months after inclusion

  15. Forgetting to take medication reported by the patient as recorded in a logbook given to the patient

    Time frame: 6 months after inclusion

  16. Perception of side effect reported by patient as noted in a logbook by the patient

    Time frame: 3 months after inclusion

  17. Perception of side effect reported by patient as noted in a logbook by the patient

    Time frame: 6 months after inclusion

  18. Effect of patients characteristics on plasma balance mean concentration in ibrutinib

    Time frame: 1 months after inclusion

  19. Effect of patients characteristics on plasma balance mean concentration in idelalisib

    Time frame: 1 months after inclusion

  20. Effect of patients genetic polymorphism on plasma balance mean concentration in idelalisib

    Time frame: 1 months after inclusion

  21. Effect of patients therapeutic target DNA polymorphism on treatment response to ibrutinib

    Time frame: Through the completion of study (24 months)

  22. Effect of patients therapeutic target DNA polymorphism on treatment response to idelalisib

    Time frame: Through the completion of study (24 months)

  23. Treatment failure rate in relation with mean concentration of ibrutinib

    Time frame: 1 month after inclusion

  24. Treatment failure rate in relation with mean concentration of idelalisib

    Time frame: 1 month after inclusion

  25. Evaluation of total exposition to ibrutinib (AUCt,ss) with residual concentration at steady state

    Time frame: Through the completion of study (24 months)

  26. Evaluation of total exposition to idelalisib (AUCt,ss) with residual concentration at steady state

    Time frame: Through the completion of study (24 months)

  27. Association of adverse event and quality of life with Short Form (36) Health Survey

    Time frame: Through the completion of study (24 months)

  28. Association of prognostic factors at inclusion and plasma balance mean concentration in ibrutinib

    Time frame: 1 month after inclusion

  29. Association of prognostic factors at inclusion and plasma balance mean concentration in idelalisib

    Time frame: 1 month after inclusion

Sponsors and collaborators

Lead sponsor

University Hospital, Toulouse

Other

Registry information

Official study 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.

Acronym: PK-E3I

Important dates

Study start
2016
Primary completion
2020
Study completion
2020
First posted
Jul 6, 2016
Registry last updated
Dec 28, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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