Montreal Immune-Related Adverse Events (MIRAE) Study

Sponsor

Sir Mortimer B. Davis - Jewish General Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05139706

Collaborator

(none)

1,000

Enrollment

Location

119.4

Anticipated Duration (Months)

8.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Immune checkpoint inhibitors (ICI) are among the most promising approaches to fighting cancer. However, a substantial percentage of patients experience off-target adverse effects in the form of mild to severe inflammation in different organs, commonly called immune-related adverse events (irAEs). irAEs can lead to treatment discontinuation, or can be life-threatening in extreme cases. The causes of irAEs are largely unknown and there are no reliable predictive biomarkers. The Montreal Immune-Related Adverse Events (MIRAE) study collects clinical information and biospecimens (blood, tissue, stool) from cancer patients treated with ICI to facilitate research on the identification of predictive biomarkers of irAEs, their causes, and the design of effective management strategies.

Condition or Disease	Intervention/Treatment	Phase
Cancer Immune System Disorder Inflammatory Reaction Autoimmune Diseases

Detailed Description

Background:

During cancer development and progression, cancer cells evolve to evade natural anti-tumor immunity. One major pathway of immune evasion involves the engagement of co-inhibitory receptors present on the surface of T cells that modulate their activation status, and therefore their ability to directly or indirectly kill tumor cells. These receptors are known as immune checkpoint inhibitors (ICI). Blockade of ICI using antibodies leads to prolonged T cell activation and unleashes the anti-tumor activity of T cells. ICI treatment for cancer has led to unprecedented advances in cancer treatment by prolonging survival of patients with previously refractory cancers. Among these ICI, CTLA-4, PD-1 and PDL-1 inhibitors have been shown to be effective cancer immunotherapies, and many other ICIs are now in pre-clinical and clinical development.

Although ICI cancer therapy is overall well tolerated, off-target immune reactions targeting healthy cells or tissues called immune-related adverse events (irAEs) develop in a substantial percentage of patients limiting the use of ICI therapy. irAEs target range from mild to severe and fatal. Currently, there are no reliable predictive biomarkers for the wide spectrum of irAEs and their clinical management in severe cases involves discontinuation of ICI therapy.

The Montreal Immune-Related Adverse Events (MIRAE) study is a biobank that collects human biological specimens (e.g., tissue, blood, plasma, PBMCs, saliva, stool) and the associated clinical information from cancer patients treated with ICI with the purpose of promoting research to identify clinical and biological predictors and mechanisms of irAEs, evaluate the effects of immunomodulatory treatment of irAEs on tumor biology, and investigate treatment strategies to minimize irAEs.

Objectives:

Identify biomarkers predictive of irAEs, including cellular, immunologic, genetic and microbial biomarkers; and
Evaluate the effects of immunomodulatory treatment of irAEs, and investigate treatment strategies that minimize irAEs and maximize ICI efficacy.

Study Design

Study Type:

Observational [Patient Registry]

Anticipated Enrollment :

1000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Montreal Database and Biorepository of Cancer Patients Treated With Immune Checkpoint Inhibitors for the Study of Immune-related Adverse Events

Actual Study Start Date :

Jan 21, 2020

Anticipated Primary Completion Date :

Jan 1, 2030

Anticipated Study Completion Date :

Jan 1, 2030

Outcome Measures

Primary Outcome Measures

Incidence of immune-related adverse events [Up to 5 years]
Biomarkers of irAE [Up to 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

= 18 years of age
cancer patients treated with ICI therapy (e.g., anti-CTLA-4, anti-PD-1, anti-PD-L1, and combinations)
patients with primary autoimmune or autoinflammatory diseases that resemble immune-related adverse events (irAEs)
healthy volunteers with non-inflammatory disorders, and without any history of cancer

Exclusion Criteria:

Participants not able to provide informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Jewish General Hospital	Montreal	Quebec	Canada	H3T 1E2

Sponsors and Collaborators

Sir Mortimer B. Davis - Jewish General Hospital

Investigators

Principal Investigator: Marie Hudson, MD, Jewish General Hospital, McGill University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Marie Hudson, MD, Marie Hudson, MD MPH FRCPC Principal Investigator, Rheumatologist, Division of Rheumatology and Department of Medicine, Jewish General Hospital and McGill University, Sir Mortimer B. Davis - Jewish General Hospital

ClinicalTrials.gov Identifier:

NCT05139706

Other Study ID Numbers:

MP-05-2019-1517

First Posted:

Dec 1, 2021

Last Update Posted:

Dec 15, 2021

Last Verified:

Nov 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Marie Hudson, MD, Marie Hudson, MD MPH FRCPC Principal Investigator, Rheumatologist, Division of Rheumatology and Department of Medicine, Jewish General Hospital and McGill University, Sir Mortimer B. Davis - Jewish General Hospital