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

Immune-related Adverse Event Clinical Trial

— PRIA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05700565
• Other study ID #: LMUKlinikum
• Status: Recruiting
• Start date: January 1, 2022
• Est. completion date: January 1, 2027

Study information

• Verified date: March 2024
• Source: LMU Klinikum
• Contact: Lucie Heinzerling
• Phone: +49 89 4400 56326
• Email: lucie.heinzerling[@]med.uni-muenchen.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: January 1, 2027
• Est. primary completion date: January 1, 2027
• Gender: All
• Age group: N/A and older

Eligibility

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.

Related Conditions & MeSH terms

• Immune-related Adverse Event

Intervention

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 immunosuppressive or immunomodulatory drugs
Other immunosuppressive or immunomodulatory drugs

Locations

Country	Name	City	State
Germany	LMU Klinikum Hauttumorzentrum	Munich

Sponsors (1)

Lead Sponsor	Collaborator
Lucie Heinzerling

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Immunophenotype	Characterisation of peripheral mononuclear blood cells	12 weeks
Secondary	Developement of grade of irAE	irAE symptoms graded according to CTCAE v5.0	12 weeks
Secondary	Patient quality of life	Quality of life assessed by EORTC QLQ-C30	12 weeks