Identification of Pathways to Mitigate Immune-Related Adverse Events With Cancer Immunotherapy

Sponsor

National Jewish Health (Other)

Overall Status

Recruiting

CT.gov ID

NCT04283539

Collaborator

(none)

238

Enrollment

Locations

Anticipated Duration (Months)

119

Patients Per Site

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This protocol is a prospective, observational study of participants receiving immunotherapy (checkpoint inhibitors, CPI) for cancer therapy, testing the hypothesis that patients with immune related cutaneous adverse events (ircAEs) have unique immunologic endotypes associated with polarized immune responses.

Condition or Disease	Intervention/Treatment	Phase
Cancer	Drug: systemic corticosteroid or biologic

Study Design

Study Type:

Observational

Anticipated Enrollment :

238 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

Identification of Pathways to Mitigate Immune-Related Adverse Events With Cancer Immunotherapy

Actual Study Start Date :

Jun 1, 2020

Anticipated Primary Completion Date :

Feb 1, 2024

Anticipated Study Completion Date :

Feb 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
CPI with ircAE Participants on check point inhibitors with immune related cutaneous adverse event	Drug: systemic corticosteroid or biologic Treatment with systemic corticosteroids or biologic therapies (for corticosteroid refractory patients or these in which corticosteroids are not the treatment of choice)
no ircAE Participants who do not have a cutaneous adverse event

Arm

Intervention/Treatment

CPI with ircAE

Participants on check point inhibitors with immune related cutaneous adverse event

Drug: systemic corticosteroid or biologic

Treatment with systemic corticosteroids or biologic therapies (for corticosteroid refractory patients or these in which corticosteroids are not the treatment of choice)

no ircAE

Participants who do not have a cutaneous adverse event

Outcome Measures

Primary Outcome Measures

Immune Biomarkers [30 days]
cytokines and chemokines

Secondary Outcome Measures

Presence of skin and circulating lipid biomarkers which occur during and after ircAEs [30 days]
Proportion of long-chain and short-chain ceramides Amounts and relative proportion of lysophosphatidylcholine molecular species. sphingosine-1-phosphate, platelet activating factor, leukotriene E4, prostaglandin F2α, endocannabinoids anandamide and 2- arachidonoylglycerol. Peripheral blood mononuclear cell RNA for expression of GRalpha, GRbeta, Vitamin D 24- Hydroxylase FK506 binding protein 5, mitogen induced kinase phosphatase 1, interleukin, tumor necrosis factor alphal
Mechanisms associated with corticosteroid unresponsiveness in patients with ircAE [12 months]
Proportion of long-chain and short-chain ceramides Amounts and relative proportion of lysophosphatidylcholine molecular species. sphingosine-1-phosphate, platelet activating factor, leukotriene E4, prostaglandin F2α, endocannabinoids anandamide and 2- arachidonoylglycerol. Peripheral blood mononuclear cell RNA for expression of GRalpha, GRbeta, Vitamin D 24- Hydroxylase FK506 binding protein 5, mitogen induced kinase phosphatase 1, interleukin, tumor necrosis factor alphal

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Provision of signed and dated informed consent form
Stated willingness to comply with all study procedures and availability for the duration of the study
Male or female, >18 yo
Diagnosis of solid tumor including, but not limited to, genitourinary/gynecologic, lung, gastrointestinal and melanoma
Receiving, or prior to starting on, a checkpoint inhibitor
Grade ≥ 2 ircAE (CTCAE v 5.0) (for cohort 1 only)
An indication for system corticosteroids or biologic therapies as determined by the treating physician (for cohort 1 only)
Life expectancy ≥ 12 weeks

Exclusion Criteria:

Daily use of systemic steroid treatment in the past 4 weeks (prednisone >10mg a day or equivalent) except for indications other than the cutaneous adverse event, and/or as an anti-emetic pre- or post-chemotherapy infusions.
Enrollment in any investigational drug trial with a drug that has not been approved
Taking other checkpoint inhibitors beyond anti-PD-(L)-1 or anti-CTLA-4 not yet indicated/approved for use
Pregnancy
Known blood borne infectious disease
Current or pervious diagnosis of a leukemia or lymphoma
Unable to give consent for study participation
Life expectancy < 12 weeks
Any other condition or diagnosis in the opinion of the investigator that would interfere with the study results

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National Jewish Health and University of Colorado Denver	Denver	Colorado	United States	80206
2	Memorial Sloan Kettering Cancer Center	New York	New York	United States	10065

Sponsors and Collaborators

National Jewish Health

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Jeffrey Kern, Professor of Medicine, National Jewish Health

ClinicalTrials.gov Identifier:

NCT04283539

Other Study ID Numbers:

ircAE HS-3411

First Posted:

Feb 25, 2020

Last Update Posted:

Sep 16, 2021

Last Verified:

Sep 1, 2021

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

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

Keywords provided by Jeffrey Kern, Professor of Medicine, National Jewish Health

checkpoint inhibitor

immuno-oncology

cutaneous adverse events

Study Results

No Results Posted as of Sep 16, 2021