PK-E3I: Association Between Side Effects Occurrence and Concentrations of Ibrutinib and Idelalisib

Sponsor
University Hospital, Toulouse (Other)
Overall Status
Completed
CT.gov ID
NCT02824159
Collaborator
(none)
121
Enrollment
1
Location
56
Duration (Months)
2.2
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
  • 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

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 Design

Study Type:
Observational
Actual Enrollment :
121 participants
Observational Model:
Cohort
Time Perspective:
Prospective
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 Start Date :
Apr 1, 2016
Actual Primary Completion Date :
Nov 1, 2020
Actual Study Completion Date :
Dec 1, 2020

Arms and Interventions

ArmIntervention/Treatment
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

Other: Blood samples for pharmacokinetics exploration
6 blood sample at regular intervals

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

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

Other: 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)

Genetic: 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

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 ...)

Outcome Measures

Primary Outcome Measures

  1. 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

  2. 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

  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 [through the end of study (24 months)]

  2. 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

  3. 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

  4. The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey [Day 1]

  5. The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey [3 months after inclusion]

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

  7. The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey [12 months after inclusion]

  8. The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey [18 months after inclusion]

  9. The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey [24 months after inclusion]

  10. Response to treatment assessed by positron emission tomography-Scan [Day 0]

    complete response, partial, stable disease, disease progression

  11. Response to treatment assessed by positron emission tomography-Scan [6 months after inclusion]

    complete response, partial, stable disease, disease progression

  12. Response to treatment assessed by positron emission tomography-Scan [12 months after inclusion]

    complete response, partial, stable disease, disease progression

  13. Response to treatment assessed by positron emission tomography-Scan [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 [3 months after inclusion]

  15. Forgetting to take medication reported by the patient as recorded in a logbook given to the patient [6 months after inclusion]

  16. Perception of side effect reported by patient as noted in a logbook by the patient [3 months after inclusion]

  17. Perception of side effect reported by patient as noted in a logbook by the patient [6 months after inclusion]

  18. Effect of patients characteristics on plasma balance mean concentration in ibrutinib [1 months after inclusion]

  19. Effect of patients characteristics on plasma balance mean concentration in idelalisib [1 months after inclusion]

  20. Effect of patients genetic polymorphism on plasma balance mean concentration in idelalisib [1 months after inclusion]

  21. Effect of patients therapeutic target DNA polymorphism on treatment response to ibrutinib [Through the completion of study (24 months)]

  22. Effect of patients therapeutic target DNA polymorphism on treatment response to idelalisib [Through the completion of study (24 months)]

  23. Treatment failure rate in relation with mean concentration of ibrutinib [1 month after inclusion]

  24. Treatment failure rate in relation with mean concentration of idelalisib [1 month after inclusion]

  25. Evaluation of total exposition to ibrutinib (AUCt,ss) with residual concentration at steady state [Through the completion of study (24 months)]

  26. Evaluation of total exposition to idelalisib (AUCt,ss) with residual concentration at steady state [Through the completion of study (24 months)]

  27. Association of adverse event and quality of life with Short Form (36) Health Survey [Through the completion of study (24 months)]

  28. Association of prognostic factors at inclusion and plasma balance mean concentration in ibrutinib [1 month after inclusion]

  29. Association of prognostic factors at inclusion and plasma balance mean concentration in idelalisib [1 month after inclusion]

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Cancer University Institute of Toulouse OncopoleToulouseFrance31059

Sponsors and Collaborators

  • University Hospital, Toulouse

Investigators

  • Principal Investigator: Loïc Ysebaert, MD, Cancer University Institute of Toulouse Oncopole

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
University Hospital, Toulouse
ClinicalTrials.gov Identifier:
NCT02824159
Other Study ID Numbers:
  • 15 7754 07
  • 2015-005572-17
First Posted:
Jul 6, 2016
Last Update Posted:
Dec 28, 2020
Last Verified:
Dec 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Undecided
Plan to Share IPD:
Undecided
Keywords provided by University Hospital, Toulouse
Additional relevant MeSH terms:

Study Results

No Results Posted as of Dec 28, 2020