Phase 1/2 Trial to determine the safety and efficacy of Extracorporeal photopheresis as treatment for steroid-refractory immune related adverse events after immune checkpoint inhibitor therapy

Phase 1

• Conditions: Immune related adverse events induced by treatment with immune checkpoint inhibitors (monoclocanl antibodies against PD-1, PD-L1 or CTLA-4)

• Registration Number: DRKS00025078
• Lead Sponsor: niversitätsklinikum Freiburg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-03-13
• Last Update Posted: 19 August 2024

Recruitment & Eligibility

• Status: Complete
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

1. Male and female patients aged =18 years with adequate German written and oral language skills
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 immunerelated adverse events as follows:
o Colitis
Diarrhea with increase of =4 stools over baseline
No improvement after 72h treatment with at least 1 mg/kg BW/day prednisolone equivalent
o 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
o 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
o 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 (WOCBP) must have a negative serum
pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within 1 week prior to the start of study drug. Males who are sexually active with WOCBP must use during the duration of the study and up to 5 months afterwards a latex or synthetic condom during any sexual contact with females of reproductive potential, even if they have undergone a successful vasectomy
Patients must abstain from donating blood, semen, or sperm during participation in the study
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. Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic 4. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
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, acid-citrate-dextrose 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
12. Inability to tolerate extracorporeal volume loss
13. Previous splenectomy
14. Pregnancy and lactation

Study & Design

• Study Type: interventional
• Study Design: Not specified