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CompletedNCT03492242CHIMeRAUpdated Sep 26, 2019

Immune CHeckpoint Inhibitors Monitoring of Adverse Drug ReAction

An observational study in Arthritis, Cancer and Cardiac Disease, sponsored by Groupe Hospitalier Pitie-Salpetriere. Completed at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2019-09-26.

Sponsored by Groupe Hospitalier Pitie-Salpetriere · Observational

Study type
Observational
Model
Case-only
Time perspective
Cross-sectional
Enrollment
1,000
Ages
18 Years and older
Sex
All
01

Study summary

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).

Read the 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.

02

Conditions studied

  • Arthritis
  • Cancer
  • Cardiac Disease
  • Endocrine System Diseases
  • Autoimmune Diseases
  • Ophthalmopathy
  • Myositis
  • Neuropathy

Keywords

  • Anti-PD-1
  • Anti-PD-L1
  • Anti-CTLA-4
  • Immune checkpoint inhibitors
  • Immune adverse drug reactions
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No
Sampling method
Non-probability sample

Study population

Patients treated with an ICI for a cancer

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

Exclusion Criteria:

  • Chronology not compatible between the drug and the toxicity
04

Study design

Observational model
Case-only
Time perspective
Cross-sectional
Enrollment
1,000 participants (actual)
Patient registry
No

Groups and cohorts

  • 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

    Drug: Immune checkpoint inhibitor

Interventions

  • DrugImmune checkpoint inhibitor

    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).

05

What researchers measure

Primary outcomes

  1. Adverse drug reactions induced by ICIs and reported in the World Health Organization (WHO) or the Base Nationale de Pharmacovigilance (BNPV)

    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).

    Time frame: Case reported in the World Health Organization (WHO) or BNPV database of individual safety case reports to May 2018

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

06

Study locations

1 site
  • AP-HP, Pitié-Salpêtrière Hospital, Department of Pharmacology, CIC-1421, Pharmacovigilance Unit, INSERM.
    Paris, 75013, France
07

References and documents

Publications

  • 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. PubMed 30819785 ↗
  • 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. PubMed 31189043 ↗
  • 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. PubMed 31118078 ↗
  • 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. PubMed 31332390 ↗
  • 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. PubMed 31390169 ↗
  • 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. PubMed 29724725 ↗
  • 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. doi: 10.1001/jamaoncol.2018.5346. PubMed 30242316 ↗
  • 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. PubMed 29698683 ↗
  • 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. PubMed 30305348 ↗
  • 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. PubMed 30359135 ↗
  • 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. PubMed 33613286 ↗
  • 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. PubMed 31678768 ↗

Individual participant data

Plan to share: Undecided

08

Registry details

Key details

Study ID
NCT03492242
Lead sponsor
Groupe Hospitalier Pitie-Salpetriere
Collaborators
Institut National de la Santé Et de la Recherche Médicale, France
Responsible party
Joe Elie Salem (Assistant director, clinical investigation center Paris Est, Groupe Hospitalier Pitie-Salpetriere) — Principal investigator
First posted
Apr 10, 2018
Start date
Feb 1, 2018
Primary completion
Sep 30, 2018
Completion
Sep 30, 2018
Last update
Sep 26, 2019

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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