- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03492242
Immune CHeckpoint Inhibitors Monitoring of Adverse Drug ReAction (CHIMeRA)
September 24, 2019 updated by: Joe Elie Salem, Groupe Hospitalier Pitie-Salpetriere
Monitoring of Immune Checkpoint Inhibitors Adverse Drug Reactions Through the WHO Vigilyze and French Pharmaco-vigilance Database (Base Nationale de Pharmacovigilance BNPV)
Immune checkpoint inhibitors (ICIs) might have high grade immune-related adverse events (irAEs) from rhumatologic, endocrinologic, cardiac or other system origin.
This study investigates reports of drug induced irAEs with treatment including anti-PD1, Anti-PDL-1, and Anti-CTLA4 classes using the World Health Organization (WHO) database VigiBase and the french database Base Nationale de PharmacoVigilance (BNPV).
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Immune checkpoint inhibitors (ICIs) have dramatically improved clinical outcomes in multiple cancer types and are increasingly being tested in earlier disease settings and used in combination.
However, immune-related adverse events (irAEs) can occur.
Here the investigators use VigiBase (http://www.vigiaccess.org/),
the World Health Organization (WHO) database of individual safety case reports, and in the Base Nationale de PharmacoVigilance (BNPV) which is the french pharmacovigilance database, to identify cases of adverse drug reaction including arthiritis, auto-immune induced diseases, cardiac diseases, endocrinologic diseases, following treatment with ICIs.
Study Type
Observational
Enrollment (Actual)
1000
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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-
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Paris, France, 75013
- AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Sampling Method
Non-Probability Sample
Study Population
Patients treated with an ICI for a cancer
Description
Inclusion Criteria:
- Case reported in the World Health Organization (WHO) database and Base Nationale de Pharmacovigilance (BNPV) of individual safety case reports to 01/05/2018
- Adverse events reported
- Patients treated with ICIs, in monotherapy or combination, included in the ATC: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).
Exclusion Criteria:
• Chronology not compatible between the drug and the toxicity
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Observational Models: Case-Only
- Time Perspectives: Cross-Sectional
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
---|---|
Adverse drug reaction induced by immune checkpoint inhibitors
Case reported in the World Health Organization (WHO) and the Base Nationale de PharmacoVigilance of patient treated by ICI, with a chronology compatible with the drug toxicity
|
Immune checkpoint inhibitor targeting either PD-1, PD-L1 or CTLA-4, and included in the following list (ATC classification) as a monotherapy or in combination: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse drug reactions induced by ICIs and reported in the World Health Organization (WHO) or the Base Nationale de Pharmacovigilance (BNPV)
Time Frame: Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
|
Identification and report of cases of adverse events associated with ICIs.
Drugs investigated are ICIs: Ipilimumab (L01XC11), Nivolumab (L01XC17), Pembrolizumab (L01XC18), Durvalumab (L01XC28), Avelumab (L01XC31), Atezolizumab (L01XC32).
|
Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Causality assessment of reported adverse drug reaction according to the WHO system
Time Frame: Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
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Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
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Description of the type of adverse drug reaction depending on the category of ICIs
Time Frame: Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
|
Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
|
Description of the other immune related adverse events concomitant to the adverse drug reaction induced by ICIs
Time Frame: Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
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Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
|
Description of the duration of treatment when the toxicity happens (role of cumulative dose)
Time Frame: Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
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Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
|
Description of the drug-drug interactions associated with adverse events
Time Frame: Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
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Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
|
Description of the pathologies (cancer) for which the incriminated drugs have been prescribed
Time Frame: Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
|
Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
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Description of the population of patients having adverse event
Time Frame: Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
|
Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General Publications
- Salem JE, Allenbach Y, Vozy A, Brechot N, Johnson DB, Moslehi JJ, Kerneis M. Abatacept for Severe Immune Checkpoint Inhibitor-Associated Myocarditis. N Engl J Med. 2019 Jun 13;380(24):2377-2379. doi: 10.1056/NEJMc1901677. No abstract available.
- Bonaca MP, Olenchock BA, Salem JE, Wiviott SD, Ederhy S, Cohen A, Stewart GC, Choueiri TK, Di Carli M, Allenbach Y, Kumbhani DJ, Heinzerling L, Amiri-Kordestani L, Lyon AR, Thavendiranathan P, Padera R, Lichtman A, Liu PP, Johnson DB, Moslehi J. Myocarditis in the Setting of Cancer Therapeutics: Proposed Case Definitions for Emerging Clinical Syndromes in Cardio-Oncology. Circulation. 2019 Jul 2;140(2):80-91. doi: 10.1161/CIRCULATIONAHA.118.034497.
- Davis EJ, Salem JE, Young A, Green JR, Ferrell PB, Ancell KK, Lebrun-Vignes B, Moslehi JJ, Johnson DB. Hematologic Complications of Immune Checkpoint Inhibitors. Oncologist. 2019 May;24(5):584-588. doi: 10.1634/theoncologist.2018-0574. Epub 2019 Feb 28.
- Johnson DB, Manouchehri A, Haugh AM, Quach HT, Balko JM, Lebrun-Vignes B, Mammen A, Moslehi JJ, Salem JE. Neurologic toxicity associated with immune checkpoint inhibitors: a pharmacovigilance study. J Immunother Cancer. 2019 May 22;7(1):134. doi: 10.1186/s40425-019-0617-x.
- Johnson DB, McDonnell WJ, Gonzalez-Ericsson PI, Al-Rohil RN, Mobley BC, Salem JE, Wang DY, Sanchez V, Wang Y, Chastain CA, Barker K, Liang Y, Warren S, Beechem JM, Menzies AM, Tio M, Long GV, Cohen JV, Guidon AC, O'Hare M, Chandra S, Chowdhary A, Lebrun-Vignes B, Goldinger SM, Rushing EJ, Buchbinder EI, Mallal SA, Shi C, Xu Y, Moslehi JJ, Sanders ME, Sosman JA, Balko JM. A case report of clonal EBV-like memory CD4+ T cell activation in fatal checkpoint inhibitor-induced encephalitis. Nat Med. 2019 Aug;25(8):1243-1250. doi: 10.1038/s41591-019-0523-2. Epub 2019 Jul 22.
- Arnaud L, Lebrun-Vignes B, Salem JE. Checkpoint inhibitor-associated immune arthritis. Ann Rheum Dis. 2019 Jul;78(7):e68. doi: 10.1136/annrheumdis-2018-213470. Epub 2018 May 3. No abstract available.
- Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, Zhao S, Das S, Beckermann KE, Ha L, Rathmell WK, Ancell KK, Balko JM, Bowman C, Davis EJ, Chism DD, Horn L, Long GV, Carlino MS, Lebrun-Vignes B, Eroglu Z, Hassel JC, Menzies AM, Sosman JA, Sullivan RJ, Moslehi JJ, Johnson DB. Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors: A Systematic Review and Meta-analysis. JAMA Oncol. 2018 Dec 1;4(12):1721-1728. doi: 10.1001/jamaoncol.2018.3923. Erratum In: JAMA Oncol. 2018 Dec 1;4(12):1792.
- Alexandre J, Moslehi JJ, Bersell KR, Funck-Brentano C, Roden DM, Salem JE. Anticancer drug-induced cardiac rhythm disorders: Current knowledge and basic underlying mechanisms. Pharmacol Ther. 2018 Sep;189:89-103. doi: 10.1016/j.pharmthera.2018.04.009. Epub 2018 Apr 24.
- Wright JJ, Salem JE, Johnson DB, Lebrun-Vignes B, Stamatouli A, Thomas JW, Herold KC, Moslehi J, Powers AC. Increased Reporting of Immune Checkpoint Inhibitor-Associated Diabetes. Diabetes Care. 2018 Dec;41(12):e150-e151. doi: 10.2337/dc18-1465. Epub 2018 Oct 10. No abstract available.
- Anquetil C, Salem JE, Lebrun-Vignes B, Johnson DB, Mammen AL, Stenzel W, Leonard-Louis S, Benveniste O, Moslehi JJ, Allenbach Y. Immune Checkpoint Inhibitor-Associated Myositis: Expanding the Spectrum of Cardiac Complications of the Immunotherapy Revolution. Circulation. 2018 Aug 14;138(7):743-745. doi: 10.1161/CIRCULATIONAHA.118.035898. No abstract available.
- Nguyen LS, Raia L, Lebrun-Vignes B, Salem JE. Graft Versus Host Disease Associated with Immune Checkpoint Inhibitors: A Pharmacovigilance Study and Systematic Literature Review. Front Pharmacol. 2021 Feb 5;11:619649. doi: 10.3389/fphar.2020.619649. eCollection 2020.
- Vozy A, De Martin E, Johnson DB, Lebrun-Vignes B, Moslehi JJ, Salem JE. Increased reporting of fatal hepatitis associated with immune checkpoint inhibitors. Eur J Cancer. 2019 Dec;123:112-115. doi: 10.1016/j.ejca.2019.09.022. Epub 2019 Nov 1. No abstract available.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
February 1, 2018
Primary Completion (Actual)
September 30, 2018
Study Completion (Actual)
September 30, 2018
Study Registration Dates
First Submitted
March 28, 2018
First Submitted That Met QC Criteria
April 3, 2018
First Posted (Actual)
April 10, 2018
Study Record Updates
Last Update Posted (Actual)
September 26, 2019
Last Update Submitted That Met QC Criteria
September 24, 2019
Last Verified
September 1, 2019
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Chemically-Induced Disorders
- Cardiovascular Diseases
- Nervous System Diseases
- Immune System Diseases
- Musculoskeletal Diseases
- Muscular Diseases
- Neuromuscular Diseases
- Heart Diseases
- Eye Diseases
- Myositis
- Drug-Related Side Effects and Adverse Reactions
- Autoimmune Diseases
- Endocrine System Diseases
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immune Checkpoint Inhibitors
Other Study ID Numbers
- CIC1421-18-06
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Undecided
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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