Pneumonitis, InterstitialNCT04807127
A Single-cell Approach to Identify Biomarkers of Pulmonary Toxicity for Immune Checkpoint Blockade
An observational study of Pneumonitis, Interstitial and Immunotherapy, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
The main goal of this prospective non-interventional exploratory monocentric study is to characterize the immune cell composition of bronchoalveolar lavage (BAL) fluid from cancer patients experiencing cancer therapy-induced pneumonitis on a single-cell scale. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Pneumonitis, Interstitial, Immunotherapy, Immune-related Adverse Events
- What is being tested?
- Immune checkpoint blockade, Targeted therapy and Radiotherapy
- Type of treatment
- Surgery or procedure
- How many people
- 60 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Feb 2020to 31 Jan 2025
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients experiencing cancer-treatment induced pneumonitis, undergoing bronchoscopy with BAL
Who may be able to join
- Adult M/F/X (>= 18 years)
- Patients receiving or having received treatment per guidelines
- Patients undergoing bronchoscopy with BAL, for possible cancer treatment-induced pneumonitis
- Not included in other clinical trials
- Signed informed consent form
Who cannot join
- Collected material not suitable for further processing in this study (e.g. bad quality). This decision will be made in consultation with a lab technician and/or bio-informatician, specialized in single-cell analysis.
Trial locations and contacts
1 site in 1 country.
Belgium1 site, 1 recruiting
- Recruiting
Universitaire Ziekenhuizen Leuven
Leuven, Flemish Brabant, 3000
Els Wauters, MD, PhD, 016340942, els.wauters@uzleuven.be
About this study
The main goal of this prospective non-interventional exploratory monocentric study is to characterize the immune cell composition of bronchoalveolar lavage (BAL) fluid from cancer patients experiencing cancer therapy-induced pneumonitis on a single-cell scale. These mechanistic insights can directly lead to putative diagnostic biomarkers and therapeutic targets.
A second highly clinically relevant hypothesis is that single-cell profiling of blood samples will reveal circulating biomarkers of ICB toxicity, making non-invasive diagnosis feasible.
Read the detailed description
The investigators will apply single cell RNA- and TCR-sequencing on up to 5,000 single cells per sample. Additionally, cell surface protein expression can be integrated with the transcriptional information. Various bioinformatics pipelines, including Seurat, will be used to identify different cell clusters, which through marker gene expression will be assigned to known cell types, cellular subtypes or phenotypes. For instance, this will make it possible to monitor the abundance of PD-1/PD-L1 expressing T-cells, cytotoxic T-cells, immune-suppressive myeloid cells etc. The following parameters at single-cell level will be relevant, amongst others:
- The composition and relative abundancies of established immune cell types (e.g. T cells (CD4+, CD8+ and regulatory subsets), NK cells, B cells, MDSCs, macrophages, neutrophils, dendritic cells). Transcriptomic data for each of these immune cell subtypes will be analyzed, allowing characterization of specific gene expression programs that define specific phenotypic states.
- Composition of all stromal cellular subtypes identified by single-cell transcriptomics.
- A gene regulatory network for each cell type and cellular subtype (or cell state) will be established and master transcriptional regulators will be identified. Individual T-cells and T-cell subclusters will be classified based on interferon activation, high rates of proliferation and transcription and increased granzyme expression, which are all indicative of T-cell activation.
Blood samples will be subjected to similar single-cell experimental procedures. First, peripheral blood mononuclear cells (PBMC) are isolated using Ficoll density gradient centrifugation. Single-cell transcriptome analysis in combination with CITE-seq will be performed on 5000 PBMC. Cellular composition will be determined using the same bioinformatic pipelines as used for processing the BAL fluid cells.
- Being tested
- Immune checkpoint blockade, Targeted therapy, Radiotherapy
- Medical subject headings
- Lung Diseases, Interstitial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Immune checkpoint blockadeDrug
Also called Pembrolizumab, Durvalumab
ICI, administered as standard-of-care treatment
Targeted therapyDrug
Also called TKI
TKI, administered as standard-of-care treatment
RadiotherapyRadiation
RT, administered as standard-of-care treatment
| Study group | Role | What they receive |
|---|---|---|
| ICI-pneumonitis | Cancer patients experiencing ICI-pneumonitis Receives: Drug: Immune checkpoint blockade | |
| Radiotherapy induced pneumonitis | Cancer patients experiencing RT-pneumonitis Receives: Radiation: Radiotherapy | |
| TKI-induced pneumonitis | Cancer patients experiencing TKI-induced pneumonitis Receives: Drug: Targeted therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Immune cell proportions, as determined by scRNA-seq, present in ICI-/RT-/TKI-induced pneumonitis BAL fluid
By identifying and statistically comparing the percentages of immune cell subtypes present in ICI-/RT-/TKI-induced pneumonitis BAL fluid, we aim to i) understand which immune processes drive these adverse events ii) identify putative molecular biomarkers iii) identify putative therapeutic targets
Measured: From date of inclusion until study completion, on average 2 years
Differentially expressed genes in BAL fluid, as determined by scRNA-seq, discriminating ICI-/RT-/TKI-induced pneumonitis
By identifying differentially expressed genes in ICI- vs. RT- vs. TKI-induced pneumonitis BAL fluid, we aim to i) understand which immune processes drive these adverse events ii) identify putative molecular biomarkers iii) identify putative therapeutic targets
Measured: From date of inclusion until study completion, on average 2 years
Secondary outcomes (2)
Immune cell proportions, as determined by scRNA-seq, present in ICI-/RT-/TKI-induced pneumonitis peripheral blood mononuclear cells
By identifying and statistically comparing the percentages of immune cell subtypes present in ICI-/RT-/TKI-induced pneumonitis peripheral blood mononuclear cells, we aim to i) understand which immune processes drive these adverse events ii) identify putative molecular biomarkers iii) identify putative therapeutic targets
Measured: From date of inclusion until study completion, on average 2 years
Differentially expressed genes in PBMC, as determined by scRNA-seq, discriminating ICI-/RT-/TKI-induced pneumonitis
By identifying differentially expressed genes in ICI- vs. RT- vs. TKI-induced pneumonitis PBMC, we aim to i) understand which immune processes drive these adverse events ii) identify putative molecular biomarkers iii) identify putative therapeutic targets
Measured: From date of inclusion until study completion, on average 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2021
- Study start1 Feb 2020
- Primary completion31 Jan 2025 (estimated)
- Study completion31 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pneumonitis, InterstitialStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- 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
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- KU Leuven
- Responsible party
- Sponsor
- Investigators
- Els Wauters, MD, PhD, Principal investigator, University Hospitals - KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04807127
- Sponsor's protocol ID
- S63357
- Status last verified
- Jun 2024
- First submitted
- 10 Mar 2021
- Last updated
- 1 Jul 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-cell Approach to Identify Biomarkers of Pulmonary Toxicity for Immune Checkpoint Blockade
- ClinicalTrials.gov ID
- NCT04807127
- Acronym / sponsor ID
- S63357
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- KU Leuven
- Study start
- 1 Feb 2020 (actual)
- Primary completion
- 31 Jan 2025 (estimated)
- Study completion
- 31 Jan 2025 (estimated)
- First posted
- 19 Mar 2021 (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.
The main goal of this prospective non-interventional exploratory monocentric study is to characterize the immune cell composition of bronchoalveolar lavage (BAL) fluid from cancer patients experiencing cancer therapy-induced pneumonitis on a single-cell scale. These mechanistic insights can directly lead to putative diagnostic biomarkers and therapeutic targets.
A second highly clinically relevant hypothesis is that single-cell profiling of blood samples will reveal circulating biomarkers of ICB toxicity, making non-invasive diagnosis feasible.
Detailed description
The investigators will apply single cell RNA- and TCR-sequencing on up to 5,000 single cells per sample. Additionally, cell surface protein expression can be integrated with the transcriptional information. Various bioinformatics pipelines, including Seurat, will be used to identify different cell clusters, which through marker gene expression will be assigned to known cell types, cellular subtypes or phenotypes. For instance, this will make it possible to monitor the abundance of PD-1/PD-L1 expressing T-cells, cytotoxic T-cells, immune-suppressive myeloid cells etc. The following parameters at single-cell level will be relevant, amongst others:
- The composition and relative abundancies of established immune cell types (e.g. T cells (CD4+, CD8+ and regulatory subsets), NK cells, B cells, MDSCs, macrophages, neutrophils, dendritic cells). Transcriptomic data for each of these immune cell subtypes will be analyzed, allowing characterization of specific gene expression programs that define specific phenotypic states.
- Composition of all stromal cellular subtypes identified by single-cell transcriptomics.
- A gene regulatory network for each cell type and cellular subtype (or cell state) will be established and master transcriptional regulators will be identified. Individual T-cells and T-cell subclusters will be classified based on interferon activation, high rates of proliferation and transcription and increased granzyme expression, which are all indicative of T-cell activation.
Blood samples will be subjected to similar single-cell experimental procedures. First, peripheral blood mononuclear cells (PBMC) are isolated using Ficoll density gradient centrifugation. Single-cell transcriptome analysis in combination with CITE-seq will be performed on 5000 PBMC. Cellular composition will be determined using the same bioinformatic pipelines as used for processing the BAL fluid cells.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| ICI-pneumonitis | – | Drug: Immune checkpoint blockadeCancer patients experiencing ICI-pneumonitis |
| Radiotherapy induced pneumonitis | – | Radiation: RadiotherapyCancer patients experiencing RT-pneumonitis |
| TKI-induced pneumonitis | – | Drug: Targeted therapyCancer patients experiencing TKI-induced pneumonitis |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients experiencing cancer-treatment induced pneumonitis, undergoing bronchoscopy with BAL
Key inclusion criteria (5 listed)
- Adult M/F/X (>= 18 years)
- Patients receiving or having received treatment per guidelines
- Patients undergoing bronchoscopy with BAL, for possible cancer treatment-induced pneumonitis
- Not included in other clinical trials
- Signed informed consent form
Key exclusion criteria (1 listed)
- Collected material not suitable for further processing in this study (e.g. bad quality). This decision will be made in consultation with a lab technician and/or bio-informatician, specialized in single-cell analysis.
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 |
|---|---|---|
| Immune checkpoint blockadeAlso: Pembrolizumab, DurvalumabICI, administered as standard-of-care treatment | Drug | ICI-pneumonitis |
| Targeted therapyAlso: TKITKI, administered as standard-of-care treatment | Drug | TKI-induced pneumonitis |
| RadiotherapyRT, administered as standard-of-care treatment | Radiation | Radiotherapy induced pneumonitis |
Primary outcome
Immune cell proportions, as determined by scRNA-seq, present in ICI-/RT-/TKI-induced pneumonitis BAL fluid
Time frame: From date of inclusion until study completion, on average 2 years
By identifying and statistically comparing the percentages of immune cell subtypes present in ICI-/RT-/TKI-induced pneumonitis BAL fluid, we aim to i) understand which immune processes drive these adverse events ii) identify putative molecular biomarkers iii) identify putative therapeutic targets
Differentially expressed genes in BAL fluid, as determined by scRNA-seq, discriminating ICI-/RT-/TKI-induced pneumonitis
Time frame: From date of inclusion until study completion, on average 2 years
By identifying differentially expressed genes in ICI- vs. RT- vs. TKI-induced pneumonitis BAL fluid, we aim to i) understand which immune processes drive these adverse events ii) identify putative molecular biomarkers iii) identify putative therapeutic targets
2 secondary outcomes
Immune cell proportions, as determined by scRNA-seq, present in ICI-/RT-/TKI-induced pneumonitis peripheral blood mononuclear cells
Time frame: From date of inclusion until study completion, on average 2 years
Differentially expressed genes in PBMC, as determined by scRNA-seq, discriminating ICI-/RT-/TKI-induced pneumonitis
Time frame: From date of inclusion until study completion, on average 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2024.
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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.
Els Wauters, MD, PhD principal investigator
University Hospitals - KU Leuven
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 Pneumonitis, Interstitial and Immunotherapy, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
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 5 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 1 Jul 2024. 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 Belgium. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Els Wauters, MD, PhD (+3216340942, els.wauters@uzleuven.be), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Immune cell proportions, as determined by scRNA-seq, present in ICI-/RT-/TKI-induced pneumonitis BAL fluid (time frame: From date of inclusion until study completion, on average 2 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 Jul 2024.