Immune Related Adverse EventsECPforIRAENCT05414552
ECP for Immune-related Adverse Events After Checkpoint Inhibitor Treatment
An observational study of Immune Related Adverse Events and Colitis, run by University of Freiburg at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Immune Related Adverse Events, Colitis, Hepatitis
- What is being tested?
- ECP
- How many people
- 11 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jun 2021to 30 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients that had develped irAEs after ICI and were treated with ECP outside of a clinical trial.
Who may be able to join
- 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
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- 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
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
Germany1 site
Medical Center - University of Freiburg Albert-Ludwigs-University Freiburg Department of Medicine I
Freiburg im Breisgau, Baden-Wurttemberg, 79106
About this study
Official title: Multicenter Retrospective Cohort Study on Patients Receiving Extracorporeal Photopheresis for Immune-related Adverse Events After Checkpoint Inhibitor Treatment
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.
Read the detailed description
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.
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
- Being tested
- ECP
- Keywords
- extracorporeal photoperesis, immune modulation, immune checkpoint inhibitor
- Medical subject headings
- Colitis, Hepatitis, Dermatitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ECPDrug
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
| Study group | Role | What they receive |
|---|---|---|
| ECP treatment arm | ECP treatment per prtocol Receives: Drug: ECP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months after end of ECP
Secondary outcomes (1)
objective response rate
objective response rate (ORR) to treatment after 6 weeks of ECP therapy
Measured: After 6 weeks of ECP therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jun 2022
- Study start1 Jun 2021
- Primary completion30 Dec 2022
- Study completion30 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Immune Related Adverse EventsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Freiburg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Robert Zeiser, University of Freiburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05414552
- Sponsor's protocol ID
- UKLFR06062022
- Acronym
- ECPforIRAE
- Status last verified
- Jul 2023
- First submitted
- 6 Jun 2022
- Last updated
- 1 Aug 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: All information and data of this retrospective analysis will be made avaible to the public.
Publications
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.
PubMed 31940706Zeiser 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.
PubMed 34260836
Study at a glance
From the registry record, last updated by the sponsor on 1 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter Retrospective Cohort Study on Patients Receiving Extracorporeal Photopheresis for Immune-related Adverse Events After Checkpoint Inhibitor Treatment
- ClinicalTrials.gov ID
- NCT05414552
- Acronym / sponsor ID
- ECPforIRAE / UKLFR06062022
- Conditions
- Immune Related Adverse Events, Colitis, Hepatitis, Dermatitis
- Keywords
- extracorporeal photoperesis, immune modulation, immune checkpoint inhibitor
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of FreiburgUniversity, hospital or other
- Study start
- 1 Jun 2021 (actual)
- Primary completion
- 30 Dec 2022 (actual)
- Study completion
- 30 Dec 2022 (actual)
- First posted
- 10 Jun 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ECP treatment arm | – | Drug: ECPECP treatment per prtocol |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients that had develped irAEs after ICI and were treated with ECP outside of a clinical trial.
Key inclusion criteria (15 listed)
- Male and female patients aged ≥18 years
- Written informed consent:
- Target population
- 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.
Key exclusion criteria (14 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ECPTreatment 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 | Drug | ECP treatment arm |
Primary outcome
Safety - treatment-related adverse events (AEs) and severe adverse events (SAEs)
Time frame: 12 months after end of ECP
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.
1 secondary outcome
objective response rate
Time frame: After 6 weeks of ECP therapy
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2023.
- Results publication: PubMed 31940706Apostolova 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.
- Results publication: PubMed 34260836Zeiser 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.
- Individual participant dataSharing planned: Yes. All information and data of this retrospective analysis will be made avaible to the public.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Immune Related Adverse Events and Colitis, run by University of Freiburg at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 1 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety - treatment-related adverse events (AEs) and severe adverse events (SAEs) (time frame: 12 months after end of ECP). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05414552, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Aug 2023.