ECP for Immune-related Adverse Events After Checkpoint Inhibitor Treatment

Study Purpose

Preliminary data demonstrate that irAEs induced by immune checkpoint blockade can be successfully treated with ECP (Apostolova et al. NEJM 2020). Therefore this clinical phase 1/2 trial is launched to validate the finding made with the individual patient in a prospective trial. The primary objective is evaluation of safety of ECP treatment in patients with irAEs. As a secondary objective, the study will determine the efficacy of ECP as a treatment for immune-related adverse events and its effect on tumor progression.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

1. Male and female patients aged ≥18 years. 2. 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. 3. 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.
4. Maximum of one additional (second line) therapy after Steroid treatment before ECP starts (e.g. infliximab for colitis) 5. 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. 6. Women must not be breastfeeding. 7. ECOG performance status 0, 1, or 2.

Exclusion Criteria:

1. 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. 2. Positive result for HIV. 3. Prior allogeneic bone marrow transplantation or prior solid organ transplantation. 4. Mechanical ventilation or patients who have resting O2 saturation <90% by pulse-oximetry. 5. Patients who require vasopressors, and/or have NYHA class III or IV heart failure. 6. Uncontrolled hypertension or ventricular arrhythmias. 7. 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. 8. 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. 9. Known allergies, hypersensitivity, or intolerance of methoxypsoralen, excipients, or similar compounds, heparin or similar compounds. 10. Aphakia. 11. 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) 12. Inability to tolerate extracorporeal volume loss. 13. Previous splenectomy. 14. Pregnancy and lactation

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05414552
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

University of Freiburg
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

N/A
Principal Investigator Affiliation N/A
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Other
Overall Status Recruiting
Countries Germany
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Immune Related Adverse Events, Colitis, Hepatitis, Dermatitis
Additional Details

Immune checkpoint inhibitors (ICI) have improved the long-term survival of patients with metastatic tumors. However, approximately 50% of the patients treated with ICI develop serious immune-related adverse events (irAE). A recent study reported that grade 3 or higher irAE occurred in 49 of 124 patients (39.5%) who received nivolumab/ipilimumab and in 41 of 123 patients (33.3%) who received nivolumab alone. Other studies report an overall frequency of grade 3-5 irAE in 24%

  • - 59% of patients treated with nivolumab 1 mg/kg body weight and ipilimumab 3 mg/kg body weight.
An incidence of 33.3% was reported when patients were treated with nivolumab 3 mg/kg body weight and ipilimumab 1 mg/kg body weight. The most common events reported during combined ICI treatment are diarrhea, rash, pruritus, hepatitis, hypothyroidism, neurological disease and pneumonitis. These numbers show that irAE are a particularly frequent complication of ICI and limit their use. Preliminary data demonstrate that irAEs induced by immune checkpoint blockade can be successfully treated with ECP (Apostolova et al. NEJM 2020). Therefore this clinical phase 1/2 trial is launched to validate the finding made with the individual patient in a prospective trial. The primary objective is evaluation of safety of ECP treatment in patients with irAEs. As a secondary objective, the study will determine the efficacy of ECP as a treatment for immune-related adverse events and its effect on tumor progression.

Arms & Interventions

Arms

Experimental: ECP treatment arm

ECP treatment per prtocol

Interventions

Drug: - ECP

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

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

International Sites

Freiburg, Baden-Württemberg, Germany

Status

Recruiting

Address

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

Freiburg, Baden-Württemberg, 79106