Treatment of Immune-related Adverse Events Refractory to Standard Therapy and Associated Changes in Immunophenotype (PRIA)

This study is an open, monocentric study. It includes patients with irAE refractory to standard therapy or patients where corticosteroids cannot be tapered. Patients will either be treated with ECP or second line immunosuppressive therapy according to investigator's choice. Patients will be followed for 24 weeks after first treatment.

Study Overview

• Status: Recruiting
• Conditions: Immune-related Adverse Event
• Intervention / Treatment: Other: Extracorporeal photopheresis; Other: Other immunosuppressive or immunomodulatory drugs

Detailed Description

At inclusion patient history including type of tumor and immunotherapy will be obtained.

At all visits symptoms, changes in concomitant medication, a medical assessment and laboratory investigations will be performed. Blood sampling for safety analysis and for investigating the immunophenotype will be performed at baseline, week 1, 4, 8 and 12.

Laboratory values assessed include:

• Complete blood count
• Chemistry including liver enzymes (AST, ALT) and total bilirubin in the case of immune-related hepatitis, CK in case of myositis, creatinine in case of nephritis
• Inflammatory markers: CRP, IL-6, Procalcitonin Peripheral blood mononuclear cells (PBMC) will be used to determine immunophenotype, including the amount of NK-cells, regulatory T- cells and myeloid-derived suppressor cells (MDSC) as well as the expression of inflammatory markers. Biological samples will be frozen for later analysis.

Additionally, patients will assess their symptoms and their quality of life by a self-administered questionnaire at baseline and week 4, 8 and 12. Quality of life will be assessed by EORTC QLQ-C30. All irAE will be graded according to CTCAE.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Lucie Heinzerling; Phone Number: +49 89 4400 56326; Email: lucie.heinzerling@med.uni-muenchen.de
• Study Contact Backup: Name: Dirk Tomsitz; Phone Number: +49 89 4400 56326; Email: dirk.tomsitz@med.uni-muenchen.de

Study Locations

• Germany
  • Munich, Germany, 80337
    • Recruiting
    • LMU Klinikum Hauttumorzentrum
    • Contact: Lucie Heinzerling, Prof. Dr.; Phone Number: +49 89 4400 56052; Email: lucie.heinzerling@med.uni-muenchen.de
    • Contact: Dirk Tomsitz, Dr.; Phone Number: +49 1525 4849311; Email: dirk.tomsitz@med.uni-muenchen.de
    • Principal Investigator: Lucie Heinzerling, Prof. Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Patients with irAE after immune checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA4 blockade) refractory to therapy with corticosteroids or inability to taper corticosteroids to prednisone equivalent <= 5mg. An irAE is defined as refractory if corticosteroids do not improve symptoms within 72 hours. The inability to taper corticosteroids is defined as relapse on standard tapering of 1 mg/kg corticosteroid over 28 days.

Description

Inclusion Criteria:

1. Subjects must we willing and able to comply with scheduled visits and must have given written informed consent.
2. irAE after immune checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA4 blockade)
3. irAE refractory to therapy with corticosteroids or inability to taper corticosteroids to prednisone equivalent <= 5mg. An irAE is defined as refractory if corticosteroids do not improve symptoms within 72 hours. The inability to taper corticosteroids is defined as relapse on standard tapering of 1 mg/kg corticosteroid over 28 days.

Exclusion Criteria:

1. Contraindications for the treatment with ECP including a known sensitivity to psoralen compounds such as 8-MOP, comorbidities that may result in photosensitivity, aphakia, history of heparin-induced thrombocytopenia, unsatisfactory cardio-circulatory function, low hematocrit values
2. Pregnancy
3. Body weight less than 40 kg.

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

Intervention / Treatment

Steroid-refractory or dependent immune-related adverse events; Immune-related adverse events (irAE) after immune checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA4 blockade) refractory to therapy with corticosteroids or inability to taper corticosteroids to prednisone equivalent <= 5mg

Other: Extracorporeal photopheresis; ECP consists of the three steps of leukapheresis, photoactivation and reinfusion and has immunomodulatory effects (modulation of dendritic cells, change in cytokine profile, induction of T cell subpopulations). Indications are currently the treatment of Sézary syndrome, Graft-versus-host disease (GvHD), organ transplant rejection and systemic scleroderma.; Other: Other immunosuppressive or immunomodulatory drugs; Other immunosuppressive or immunomodulatory drugs

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunophenotype	Characterisation of peripheral mononuclear blood cells	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Developement of grade of irAE	irAE symptoms graded according to CTCAE v5.0	12 weeks
Patient quality of life	Quality of life assessed by EORTC QLQ-C30	12 weeks

Collaborators and Investigators

• Sponsor: Lucie Heinzerling
• Investigators: Principal Investigator: Lucie Heinzerling, Department of Dermatology and Allergy, University Hospital, LMU Munich

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: November 4, 2022
• First Submitted That Met QC Criteria: January 17, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 13, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Steroid-refractory; Steroid-dependent
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Immunosuppressive Agents; Immunomodulating Agents
• Other Study ID Numbers: LMUKlinikum

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