Extracorporeal photopheresis as treatment for immune related adverse events after immunotherapy

Phase 1

• Conditions: Immune related adverse events induced by treatment with immune checkpoint inhibitors (monoclocanl antibodies against PD-1, PD-L1 or CTLA-4); MedDRA version: 21.1Level: LLTClassification code 10043408Term: Therapeutic agent toxicitySystem Organ Class: 10022117 - Injury, poisoning and procedural complications; MedDRA version: 26.1Level: LLTClassification code 10067033Term: Drug side effectSystem Organ Class: 10018065 - General disorders and administration site conditions; MedDRA version: 24.0Level: PTClassification code 10061623Term: Adverse drug reactionSystem Organ Class: 10018065 - General disorders and administration site conditions; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2021-002073-26-DE
• Lead Sponsor: Medical Center - University of Freiburg

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-02-10
• Last Update Posted: 5 August 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

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. 30% of the patients that will be included should have non-skin cancer.
•Patients should have clinical and/or histological evidence of immune-related adverse events as follows:
oColitis
?Diarrhea with increase of =4 stools over baseline
?No improvement after 72h treatment with at least 1 mg/kg BW/day prednisolone equivalent
ooHepatitis
?Alanine aminotransferase and/or aspartate aminotransferase =3x ULN if baseline was normal; or =3x baseline if baseline was abnormal and/or total bilirubin >1.5 ULN.
?No improvement after 72h treatment with at least 1 mg/kg BW/day prednisolone equivalent
oPneumonitis
?Radiographic changes that involve more than one lobe of the lung or =25% of lung parenchyma and new symptoms such as cough, dyspnea or chest painor new oxygen therapy
?No improvement after 72h treatment with 1 mg/kg BW/day prednisolone equivalent
oDermatitis
?Skin erythema, maculopapular or pustulopapular rRash covering >=30% of the body surface area and moderate or severe symptoms
?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 (see also 10.9). 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

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 6

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.Sexually active men and 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 last ECP procedure (see also 10.9
12.Inability to tolerate extracorporeal volume loss
13.Previous splenectomy
14.Pregnancy and lactation

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified