ECP for Immune-related Adverse Events After Checkpoint Inhibitor Treatment

NCT05414552 | Completed

• 1 other identifier: UKLFR06062022
• Study Type: observational
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Preliminary data demonstrate that irAEs induced by immune checkpoint blockade can be successfully treated with ECP (Apostolova et al. NEJM 2020). Therefore this retrospective analysis is launched to validate the finding made with the individual patient in a larger patient cohort. The analysis will include the evaluation of safety of ECP treatment in patients with irAEs and collect data on the efficacy of ECP as a treatment for immune-related adverse events and its effect on tumor progression.

Conditions

Immune Related Adverse Events; Colitis; Hepatitis; Dermatitis

Keywords

extracorporeal photoperesis; immune modulation; immune checkpoint inhibitor

Outcome Measures

Primary Outcomes (1)

• Safety - treatment-related adverse events (AEs) and severe adverse events (SAEs)

  To evaluate the rate of treatment-related adverse events (AEs) and severe adverse events (SAEs) in patients treated with ECP for immune-checkpoint inhibitor-induced colitis, pneumonitis, hepatitis or dermatitis.

  12 months after end of ECP

Secondary Outcomes (1)

• objective response rate

  After 6 weeks of ECP therapy

Study Arms (1)

ECP treatment arm

ECP treatment per prtocol

Drug: ECP

Interventions

ECP DRUG

Treatment with ECP for irAEs with 2 cycles performed on two consecutive days, for the first 4 weeks repeated every week, and from week 5 to 12 repeated every two weeks

ECP treatment arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients that had develped irAEs after ICI and were treated with ECP outside of a clinical trial.

You may qualify if:

• Male and female patients aged ≥18 years
• Written informed consent:
• Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines.
• Subjects must be able to understand and willing to comply with scheduled visits, treatment schedule, laboratory tests and mandatory collection of blood, and other requirements of the study.
• Subject Re-enrollment: This trial permits the re-enrollment of a subject that has discontinued the study as a screening failure. If re-enrolled, the subject must be re-consented.
• Target population
• Patients who have received treatment with an anti-PD-1, anti-PD-L1 or an anti-CTLA-4 antibody or any combination of these for any type of malignancy in the last 24 months before screening.
• Patients should have clinical and/or histological evidence of immune-related adverse events as follows:
• Colitis Diarrhea with increase of ≥4 stools over baseline No improvement after 72h treatment with at least 1 mg/kg BW/day prednisolone equivalent
• Hepatitis Alanine aminotransferase and/or aspartate aminotransferase ≥3x ULN if baseline was normal; or ≥3x baseline if baseline was abnormal No improvement after 72h treatment with at least 1 mg/kg BW/day prednisolone equivalent
• Pneumonitis Radiographic changes and new symptoms such as cough, dyspnea or chest pain No improvement after 72h treatment with 1 mg/kg BW/day prednisolone equivalent Dermatitis Skin erythema, maculopapular or pustulopapular rash covering ≥30% of the body surface area No improvement after 72h treatment with at least 1 mg/kg BW/day prednisolone equivalent
• Maximum of one additional (second line) therapy after Steroid treatment before ECP starts (e.g. infliximab for colitis)
• Women of childbearing potential must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 1 week prior to the start of study drug.
• Women must not be breastfeeding.
• ECOG performance status 0, 1, or 2

You may not qualify if:

• Active treatment in a clinical study of any investigational agent within 14 days prior day 0 or within 5 half-lives of the study treatment, whichever is greater.
• Positive result for HIV.
• Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• Mechanical ventilation or patients who have resting O2 saturation \<90% by pulse-oximetry.
• Patients who require vasopressors, and/or have NYHA class III or IV heart failure.
• Uncontrolled hypertension or ventricular arrhythmias.
• Previous or concurrent malignancies within the last 3 years of enrollment other than the disease for which checkpoint-inhibitor blockade was applied. Exceptions are adequately treated basal or squamous cell skin cancer, or any other cancer from which the subject has been disease-free for more than 3 years.
• Any condition that would, in the investigator's judgment, interfere with full participation in the study, including administration of study drug and attending required study visits; pose a significant risk to the subject; or interfere with interpretation of study data
• Known allergies, hypersensitivity, or intolerance of methoxypsoralen, excipients, or similar compounds, heparin or similar compounds
• Aphakia
• Female patients of child-bearing potential who are not willing to use highly effective methods of contraception during the trial and at least 5 months after the ECP procedure (see also 10.9)
• Inability to tolerate extracorporeal volume loss
• Previous splenectomy
• Pregnancy and lactation

Sponsors & Collaborators

• University of Freiburg: lead

Study Sites (1)

Medical Center - University of Freiburg Albert-Ludwigs-University Freiburg Department of Medicine I

Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

Location

Related Publications (2)

• Apostolova P, Unger S, von Bubnoff D, Meiss F, Becher B, Zeiser R. Extracorporeal Photopheresis for Colitis Induced by Checkpoint-Inhibitor Therapy. N Engl J Med. 2020 Jan 16;382(3):294-296. doi: 10.1056/NEJMc1912274. No abstract available.

  PMID: 31940706 RESULT

• Zeiser R, Polverelli N, Ram R, Hashmi SK, Chakraverty R, Middeke JM, Musso M, Giebel S, Uzay A, Langmuir P, Hollaender N, Gowda M, Stefanelli T, Lee SJ, Teshima T, Locatelli F; REACH3 Investigators. Ruxolitinib for Glucocorticoid-Refractory Chronic Graft-versus-Host Disease. N Engl J Med. 2021 Jul 15;385(3):228-238. doi: 10.1056/NEJMoa2033122.

  PMID: 34260836 RESULT

MeSH Terms

Conditions

Colitis; Hepatitis; Dermatitis

Condition Hierarchy (Ancestors)

Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases; Liver Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 6, 2022
• First Posted: June 10, 2022
• Study Start: June 1, 2021
• Primary Completion: December 30, 2022
• Study Completion: December 30, 2022
• Last Updated: August 1, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The data will be made available after publication ofthe manuscript and from then on infinitively.

Locations

DE (1)