Autoimmunity After Checkpoint Blockade

Mechanisms of Immunotoxicology in Cancer Patients

The purpose of this study is to better understand how the treatment of cancer with immune checkpoint inhibitors (ICI) leads to the development of autoimmunity. Specifically, we wish to understand the genetics and immune system features that cause a subset of cancer patients treated with checkpoint inhibitor therapy to develop an immune-related adverse event (irAE).

Study Overview

• Status: Recruiting
• Conditions: Cancer; Oncology; Autoimmunity; Immunotoxicity

Detailed Description

The goal of this study is to understand how the treatment of cancer with checkpoint inhibitors leads to the development of autoimmunity. Specifically, to understand the genetics and immune system features that cause a subset of cancer patients treated with checkpoint inhibitors to develop autoimmunity. At least 300 patients will be enrolled when they are initially prescribed any checkpoint inhibitor. Peripheral blood and serum from patients when they enroll and examine the genetics, serum factors, and phenotype of the immune system. There is no planned intervention. Subjects will be asked to provide peripheral blood and serum at established time points when they are getting therapeutic infusions and routine clinical labs, as well as, at the time they develop any autoimmune symptoms. Urine may also be collected at the time of enrollment, standard study visits, and/or at the time of an autoimmune complication. Inclusion criteria include a diagnosis of cancer, prescription for a checkpoint inhibitor, and fluency in English. Exclusion criteria include any subjects not willing or able to give consent, children under the age of 18, and history of transplant. There will not be any interventions. Clinical data will be extracted from electronic medical records. Coded data will be stored in a REDCap database. PHI and study key stored at UPenn on a password-protected database on an encrypted drive that is institutionally secured and managed by the University of Pennsylvania.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Kyra J Sacksith; Phone Number: 215-898-9339; Email: kyra.sacksith@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania - Abramson Cancer Center
      • Contact: Kyra J Sacksith

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults who are able to consent to the study and are identified by their physician or a clinical coordinator to receive an immune checkpoint inhibitor for the treatment of cancer.

Description

Inclusion Criteria:

• A diagnosis of cancer and prescription for a checkpoint inhibitor

Exclusion Criteria:

• Any subjects not willing or able to give consent
• Children under the age of 18
• A history of transplant

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Study Population; Adult patients with a diagnosis of cancer receiving checkpoint inhibitor therapy at the University of Pennsylvania's Abramson Cancer Center (ACC).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The phenotype and function of peripheral blood cells (i.e., CD4+ T cells, CD8+ T cells, B cells, myeloid cells) characteristic to patients receiving checkpoint inhibitor therapy.	The phenotypic analysis will include multiple surface markers that define populations of cells, including activated, memory, and regulatory populations. Cells will also be activated to determine which cytokines are produced.	3 years
The prevalence of immune-related adverse events (irAEs) that complicate checkpoint inhibitor therapy.	This is a pilot analysis to better understand how the treatment of cancer with immune checkpoint inhibitors leads to the development of autoimmunity in a subset of cancer patients.	3 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The number of future research studies and/or collaborations resulting directly from the databank of tissues and other relevant clinical information that will be established.	To facilitate collaborations between research groups from diverse disciplines that enables rapid translation of ongoing and future basic research findings that leads to individualized, or personalized care for patients receiving immunotherapies.	3 years

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Terri M Laufer, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): February 24, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: September 23, 2019
• First Submitted That Met QC Criteria: October 7, 2019
• First Posted (Actual): October 8, 2019

Study Record Updates

• Last Update Posted (Actual): February 14, 2024
• Last Update Submitted That Met QC Criteria: February 13, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases
• Other Study ID Numbers: 832823

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: No
• Studies a U.S. FDA-regulated device product: No