Ignite Creation Date:
2025-12-24 @ 2:58 PM
Ignite Modification Date:
2026-03-04 @ 2:24 AM
Study NCT ID:
NCT02824159
Status:
COMPLETED
Last Update Posted:
2020-12-28
First Post:
2016-06-30
Is Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Association Between Side Effects Occurrence and Concentrations of Ibrutinib and Idelalisib
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D019337', 'term': 'Hematologic Neoplasms'}], 'ancestors': [{'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D001800', 'term': 'Blood Specimen Collection'}, {'id': 'D012149', 'term': 'Restraint, Physical'}], 'ancestors': [{'id': 'D013048', 'term': 'Specimen Handling'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D011677', 'term': 'Punctures'}, {'id': 'D013514', 'term': 'Surgical Procedures, Operative'}, {'id': 'D008919', 'term': 'Investigative Techniques'}, {'id': 'D032763', 'term': 'Behavior Control'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D007103', 'term': 'Immobilization'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITH_DNA', 'description': 'Samples to be collected are :\n\n* Blood samples for dosage of drug in plasma (No DNA)\n* Blood samples (genetic profile of drug elimination and presence of treatment resistance mutation) and saliva samples (genetic profile drug elimination )'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'COHORT'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 121}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2016-04'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2020-12', 'completionDateStruct': {'date': '2020-12', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2020-12-24', 'studyFirstSubmitDate': '2016-06-30', 'studyFirstSubmitQcDate': '2016-06-30', 'lastUpdatePostDateStruct': {'date': '2020-12-28', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2016-07-06', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2020-11', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Evaluation of clinically significant side effect occurence with plasma balance mean concentration in ibrutinib', 'timeFrame': '1 months after treatment initiation', 'description': 'Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit'}, {'measure': 'Evaluation of clinically significant side effect occurence with plasma balance mean concentration in idelalisib', 'timeFrame': '1 months after treatment initiation', 'description': 'Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit'}], 'secondaryOutcomes': [{'measure': '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', 'timeFrame': 'through the end of study (24 months)'}, {'measure': 'Plasma balance mean concentration in ibrutinib with collection of blood samples', 'timeFrame': '1 month after inclusion', 'description': 'Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit'}, {'measure': 'Plasma balance mean concentration in idelalisib with collection of blood samples', 'timeFrame': '1 month after inclusion', 'description': 'Plasma balance mean will be calculated with 6 blood samples collected at regular intervals during the visit'}, {'measure': 'The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey', 'timeFrame': 'Day 1'}, {'measure': 'The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey', 'timeFrame': '3 months after inclusion'}, {'measure': 'The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey', 'timeFrame': '6 months after inclusion'}, {'measure': 'The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey', 'timeFrame': '12 months after inclusion'}, {'measure': 'The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey', 'timeFrame': '18 months after inclusion'}, {'measure': 'The health-related quality (HRQoL) by the self-reported French version of the Short Form (36) Health Survey', 'timeFrame': '24 months after inclusion'}, {'measure': 'Response to treatment assessed by positron emission tomography-Scan', 'timeFrame': 'Day 0', 'description': 'complete response, partial, stable disease, disease progression'}, {'measure': 'Response to treatment assessed by positron emission tomography-Scan', 'timeFrame': '6 months after inclusion', 'description': 'complete response, partial, stable disease, disease progression'}, {'measure': 'Response to treatment assessed by positron emission tomography-Scan', 'timeFrame': '12 months after inclusion', 'description': 'complete response, partial, stable disease, disease progression'}, {'measure': 'Response to treatment assessed by positron emission tomography-Scan', 'timeFrame': '24 months after inclusion', 'description': 'complete response, partial, stable disease, disease progression'}, {'measure': 'Forgetting to take medication reported by the patient as recorded in a logbook given to the patient', 'timeFrame': '3 months after inclusion'}, {'measure': 'Forgetting to take medication reported by the patient as recorded in a logbook given to the patient', 'timeFrame': '6 months after inclusion'}, {'measure': 'Perception of side effect reported by patient as noted in a logbook by the patient', 'timeFrame': '3 months after inclusion'}, {'measure': 'Perception of side effect reported by patient as noted in a logbook by the patient', 'timeFrame': '6 months after inclusion'}, {'measure': 'Effect of patients characteristics on plasma balance mean concentration in ibrutinib', 'timeFrame': '1 months after inclusion'}, {'measure': 'Effect of patients characteristics on plasma balance mean concentration in idelalisib', 'timeFrame': '1 months after inclusion'}, {'measure': 'Effect of patients genetic polymorphism on plasma balance mean concentration in idelalisib', 'timeFrame': '1 months after inclusion'}, {'measure': 'Effect of patients therapeutic target DNA polymorphism on treatment response to ibrutinib', 'timeFrame': 'Through the completion of study (24 months)'}, {'measure': 'Effect of patients therapeutic target DNA polymorphism on treatment response to idelalisib', 'timeFrame': 'Through the completion of study (24 months)'}, {'measure': 'Treatment failure rate in relation with mean concentration of ibrutinib', 'timeFrame': '1 month after inclusion'}, {'measure': 'Treatment failure rate in relation with mean concentration of idelalisib', 'timeFrame': '1 month after inclusion'}, {'measure': 'Evaluation of total exposition to ibrutinib (AUCt,ss) with residual concentration at steady state', 'timeFrame': 'Through the completion of study (24 months)'}, {'measure': 'Evaluation of total exposition to idelalisib (AUCt,ss) with residual concentration at steady state', 'timeFrame': 'Through the completion of study (24 months)'}, {'measure': 'Association of adverse event and quality of life with Short Form (36) Health Survey', 'timeFrame': 'Through the completion of study (24 months)'}, {'measure': 'Association of prognostic factors at inclusion and plasma balance mean concentration in ibrutinib', 'timeFrame': '1 month after inclusion'}, {'measure': 'Association of prognostic factors at inclusion and plasma balance mean concentration in idelalisib', 'timeFrame': '1 month after inclusion'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['ibrutinib', 'idelalisib', 'side effect', 'pharmacokinetic', 'plasma balance mean concentration'], 'conditions': ['Hematological Malignancies']}, 'referencesModule': {'references': [{'pmid': '39037964', 'type': 'DERIVED', 'citation': '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': '32328976', 'type': 'DERIVED', 'citation': '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.'}]}, 'descriptionModule': {'briefSummary': '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.\n\nClinical 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.', 'detailedDescription': '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.\n\nPharmacokinetic 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.\n\nTo 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.\n\nEvery 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'Patients with haematologic malignancies', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Evidence of Chronic Lymphocytic Leukaemia (CLL), or Follicular Lymphoma (FL) or Mantle cell lymphoma (MCL) and a first prescription of idelalisib or ibrutinib\n* Patients must give written informed consent\n* Patients with Health Insurance System\n\nExclusion Criteria:\n\n* Patient who several blood tests can't be performed (poor venous access)\n* Patients under legal guardian\n* Pregnant or breastfeeding women"}, 'identificationModule': {'nctId': 'NCT02824159', 'acronym': 'PK-E3I', 'briefTitle': 'Association Between Side Effects Occurrence and Concentrations of Ibrutinib and Idelalisib', 'organization': {'class': 'OTHER', 'fullName': 'University Hospital, Toulouse'}, 'officialTitle': '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.', 'orgStudyIdInfo': {'id': '15 7754 07'}, 'secondaryIdInfos': [{'id': '2015-005572-17', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'label': 'Patient with haematologic malignancies', 'description': 'Interventions to be administrated are :\n\n* Clinical examinations\n* Biological statement\n* Blood samples for pharmacokinetics exploration\n* Imagery with positron emission tomography scan or resonance magnetic imagery\n* Saliva samples for genetics analyses\n* Blood samples for treatment mutation resistance search\n* Quality of life scale questionary\n* Detection of adverse events', 'interventionNames': ['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': [{'name': 'Blood samples for pharmacokinetics exploration', 'type': 'OTHER', 'description': '6 blood sample at regular intervals', 'armGroupLabels': ['Patient with haematologic malignancies']}, {'name': 'Imagery', 'type': 'OTHER', 'description': 'Efficacity will be assessed with 3 sessions of resonance magnetic imaging or positron emission tomography scan', 'armGroupLabels': ['Patient with haematologic malignancies']}, {'name': 'Quality of life scale', 'type': 'OTHER', 'description': 'Quality of life will be evaluated with questionaries 5 times during the study', 'armGroupLabels': ['Patient with haematologic malignancies']}, {'name': 'Detection of adverse events', 'type': 'OTHER', 'description': 'The detection will be assessed using the AMA (assistance des malades ambulatoires) system', 'armGroupLabels': ['Patient with haematologic malignancies']}, {'name': 'Saliva samples', 'type': 'GENETIC', 'description': 'Saliva samples will be collected to explore genetic characteristics of germinal DNA (genes involved in drug pharmacokinetic)', 'armGroupLabels': ['Patient with haematologic malignancies']}, {'name': 'Blood sample', 'type': 'GENETIC', 'description': 'A unique blood sample will be performed in order to determine characteristics of tumoral DNA (resistance to treatment mutation)', 'armGroupLabels': ['Patient with haematologic malignancies']}, {'name': 'Biological statement', 'type': 'OTHER', 'description': 'The following parameters will be assessed :\n\n* Complete blood count\n* Hemoglobin\n* Hepatic enzymes\n* Creatinine clearance\n* Lactate dehydrogenase rate\n* Total bilirubin rate\n* Cluster of differentiation 4 T lymphocytes rate\n* Total gamma-globulins rate', 'armGroupLabels': ['Patient with haematologic malignancies']}, {'name': 'Clinical examination', 'type': 'OTHER', 'description': 'The clinical examination are composed by :\n\n* Weigh, Height and body mass index measurement\n* Clinical state of patient during examination\n* Stage of the disease (OMS grade, binet classification, Ahn Arbor classification)\n* Presence of B symptomatology\n* Prognostic factors (Genetic, Mantle Cell Lymphoma International Prognostic Index, Follicular Lymphoma International Prognostic Index, presence of lymph nodes, other target organs ...)', 'armGroupLabels': ['Patient with haematologic malignancies']}]}, 'contactsLocationsModule': {'locations': [{'zip': '31059', 'city': 'Toulouse', 'country': 'France', 'facility': 'Cancer University Institute of Toulouse Oncopole', 'geoPoint': {'lat': 43.60426, 'lon': 1.44367}}], 'overallOfficials': [{'name': 'Loïc Ysebaert, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Cancer University Institute of Toulouse Oncopole'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'UNDECIDED'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University Hospital, Toulouse', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}