A Single-cell Approach to Identify Biomarkers of Pulmonary Toxicity for Immune Checkpoint Blockade

NCT04807127 | Recruiting DMC

• 1 other identifier: S63357
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Pneumonitis, Interstitial; Immunotherapy; Immune-related Adverse Events

Outcome Measures

Primary Outcomes (2)

• 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

  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

  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

  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

  From date of inclusion until study completion, on average 2 years

Study Arms (3)

ICI-pneumonitis

Cancer patients experiencing ICI-pneumonitis

Drug: Immune checkpoint blockade

Radiotherapy induced pneumonitis

Cancer patients experiencing RT-pneumonitis

Radiation: Radiotherapy

TKI-induced pneumonitis

Cancer patients experiencing TKI-induced pneumonitis

Drug: Targeted therapy

Interventions

Immune checkpoint blockade DRUG

ICI, administered as standard-of-care treatment

Also known as: Pembrolizumab, Durvalumab

ICI-pneumonitis

Targeted therapy DRUG

TKI, administered as standard-of-care treatment

Also known as: TKI

TKI-induced pneumonitis

Radiotherapy RADIATION

RT, administered as standard-of-care treatment

Radiotherapy induced pneumonitis

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients experiencing cancer-treatment induced pneumonitis, undergoing bronchoscopy with BAL

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead
• KU Leuven: collaborator

Study Sites (1)

Universitaire Ziekenhuizen Leuven

Leuven, Flemish Brabant, 3000, Belgium

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

* BAL samples will not be retained * PBMC samples will be stored at -80°C, for batch processing

MeSH Terms

Conditions

Lung Diseases, Interstitial

Interventions

Immune Checkpoint Inhibitors; pembrolizumab; durvalumab; Radiotherapy

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses; Therapeutics

Study Officials

• Els Wauters, MD, PhD

  University Hospitals - KU Leuven

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Els Wauters, MD, PhD

CONTACT

+3216340942; els.wauters@uzleuven.be

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2021
• First Posted: March 19, 2021
• Study Start: February 1, 2020
• Primary Completion: January 31, 2025
• Study Completion: January 31, 2025
• Last Updated: July 1, 2024

Record last verified: 2024-06

Locations

BE (1)