Association Between Side Effects Occurrence and Concentrations of Ibrutinib and Idelalisib

NCT02824159 | Completed

• 2 other identifiers: 15 7754 072015-005572-17
• Study Type: observational
• Target: 121
• Locations: 1 country
• Sites: 1

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.

Conditions

Hematological Malignancies

Keywords

ibrutinib; idelalisib; side effect; pharmacokinetic; plasma balance mean concentration

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (29)

• 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 concentration in idelalisib with collection of blood samples

  1 month after inclusion

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

  Day 1

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

  3 months after inclusion

Study Arms (1)

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; Other: Imagery; Other: Quality of life scale; Other: Detection of adverse events; Genetic: Saliva samples; Genetic: Blood sample; Other: Biological statement; Other: Clinical examination

Interventions

Blood samples for pharmacokinetics exploration OTHER

6 blood sample at regular intervals

Patient with haematologic malignancies

Imagery OTHER

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

Patient with haematologic malignancies

Quality of life scale OTHER

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

Patient with haematologic malignancies

Detection of adverse events OTHER

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

Patient with haematologic malignancies

Saliva samples GENETIC

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

Patient with haematologic malignancies

Blood sample GENETIC

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

Patient with haematologic malignancies

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

Patient with haematologic malignancies

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 ...)

Patient with haematologic malignancies

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with haematologic malignancies

You may qualify if:

• 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

You may not qualify if:

• Patient who several blood tests can't be performed (poor venous access)
• Patients under legal guardian
• Pregnant or breastfeeding women

Sponsors & Collaborators

• University Hospital, Toulouse: lead

Study Sites (1)

Cancer University Institute of Toulouse Oncopole

Toulouse, 31059, France

Location

Related Publications (2)

• 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.

  PMID: 39037964 DERIVED

• 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.

  PMID: 32328976 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Samples to be collected are : * Blood samples for dosage of drug in plasma (No DNA) * Blood samples (genetic profile of drug elimination and presence of treatment resistance mutation) and saliva samples (genetic profile drug elimination )

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Blood Specimen Collection; Restraint, Physical

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Behavior Control; Therapeutics; Immobilization

Study Officials

• Loïc Ysebaert, MD

  Cancer University Institute of Toulouse Oncopole

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2016
• First Posted: July 6, 2016
• Study Start: April 1, 2016
• Primary Completion: November 1, 2020
• Study Completion: December 1, 2020
• Last Updated: December 28, 2020

Record last verified: 2020-12

Locations

FR (1)