Extracorporeal photopheresis as treatment for immune related adverse events after immunotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical Center - University Of Freiburg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

27 Jul 2022 → 23 Oct 2025

Decision date (initial)

2024-08-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Mallinckrodt Pharmaceuticals

External identifiers

EU CT number

2024-513614-36-00

EudraCT number

2021-002073-26

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

Our preliminary data demonstrate that irAEs induced by immune
checkpoint blockade can be successfully treated with ECP (Apostolova et
al. NEJM 2020). We therefore intend to launch a clinical phase 1/2 trial
to validate this finding in a prospective trial. The primary objective is
evaluation of safety of ECP treatment in patients with irAEs.

Secondary objectives 1

1. • As a secondary objective, we will determine the efficacy of ECP as a XML File Identifier: gEI09IdZbHieAOfxaGDFNjDvRPY= Page 11/25 treatment for immune-related adverse events and its effect on tumor progression. • To evaluate the investigator-assessed objective response rate (ORR) to treatment after 6 and 12 weeks of ECP therapy The response criteria for each organ are described in chapter 6.2. • To assess time to response • To assess the duration of investigator-assessed clinical response • To assess overall survival (OS) at 1 year after end of ECP treatment • To measure the time to complete discontinuation of other immunosuppressive therapy • To assess changes in immune cell phenotype and metabolism during treatment • To assess the relapse rates of irAEs upon discontinuation of ECP and rechallenge with an immune checkpoint inhibitor • To assess the incidence of tumor progression or relapse

Conditions and MedDRA coding

Immune related adverse events induced by treatment with immunotherapy

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Male and female patients aged ≥18 years with adequate German written and oral language skills
2. 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 reenrolled, the subject must be re-consented.
3. 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 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 o Hepatitis  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 o Pneumonitis  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 o Dermatitis  Skin erythema, maculopapular or pustulopapular rRash covering >≥ 30% of the body surface area and moderate or severe symptoms  No improvement after
4. 4. Maximum of one additional (second line) therapy after Steroid treatment before ECP starts (e.g. infliximab for colitis)
5. 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. 6. Women must not be breastfeeding.
7. 7. ECOG performance status 0, 1, or 2

Exclusion criteria 14

1. 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. 2. Positive result for HIV.
3. 3. Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic
4. 4. Prior allogeneic bone marrow transplantation or prior solid organ transplantation.
5. 5. Patients who require vasopressors, and/or have NYHA class III or IV heart failure.
6. 6. Uncontrolled hypertension or ventricular arrhythmias.
7. 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. 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. 9. Known allergies, hypersensitivity, or intolerance of methoxypsoralen, excipients, or similar compounds, acid-citrate-dextrose or similar compounds
10. 10. Aphakia
11. 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. 12. Inability to tolerate extracorporeal volume loss
13. 13. Previous splenectomy
14. 14. Pregnancy and lactation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. To evaluate the rate of treatment-related adverse events (AEs) and serious adverse events (SAEs) in patients treated with ECP for immunecheckpoint inhibitor-induced colitis, pneumonitis, hepatitis or dermatitis. A positive result from the study is defined as ≤50% of the patients developing a treatment-related SAE.

Secondary endpoints 1

1. Key secondary endpoints: • To evaluate the investigator-assessed objective response rate (ORR) to treatment after 6 and 12 weeks of ECP therapy The response criteria for each organ are described in chapter 6.2. • To assess time to response • To assess the duration of investigator-assessed clinical response • To assess overall survival (OS) at 1 year after end of ECP treatment • To measure the time to complete discontinuation of other immunosuppressive therapy

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical Center - University Of Freiburg

Sponsor organisation

Medical Center - University Of Freiburg

Address

Breisacher Strasse 153, Mooswald Mooswald

City

Freiburg Im Breisgau

Postcode

79110

Country

Germany

Scientific contact point

Organisation

Medical Center - University Of Freiburg

Contact name

Prof. Robert Zeiser

Public contact point

Organisation

Medical Center - University Of Freiburg

Contact name

ECTU

Locations

1 EU/EEA country · 3 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications