Clinical trial NCT05700565: Treatment of Immune-related Adverse Events Refractory to Standard Therapy and Associated Changes in Immunophenotype
Official title: Treatment of Immune-related Adverse Events Refractory to Standard Therapy and Associated Changes in Immunophenotype
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Immune-related Adverse Event
Keywords: Steroid-refractory
Steroid-dependent
Lead sponsor: LMU Klinikum
Sponsor class: OTHER
First posted: 2023-01-26
Enrollment: 50
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Immunophenotype
timeFrame: 12 weeks
Secondary outcomes:
measure: Developement of grade of irAE
timeFrame: 12 weeks
measure: Patient quality of life
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Munich
country: Germany
facility: LMU Klinikum Hauttumorzentrum
Study officials:
affiliation: Department of Dermatology and Allergy, University Hospital, LMU Munich
name: Lucie Heinzerling
role: PRINCIPAL_INVESTIGATOR
References: