The Clinical Implications of Immune Checkpoint Pathways in PCNSL

NCT04158128 | Completed

• 1 other identifier: 201608069RINB
• Study Type: observational
• Target: 46
• Locations: 1 country
• Sites: 1

Brief Summary

Central nervous system lymphoma (CNSL) is a rare brain tumor constituting 3% of all newly diagnosed brain tumors, and 2% to 3% of all cases of non-Hodgkin lymphoma. There are two subtypes of CNSL. Owing to its low incidence, there is limited prospective and/or randomized data to guide the therapy of CNSL. Current knowledge about optimal diagnostic, prognostic and therapeutic strategies of CNSL is urged. The immune system plays a fundamental role in controlling and eradicating cancer but is held in check by inhibitory receptors and ligands. These immune checkpoint pathways, which normally maintain self-tolerance and limit collateral tissue damage during anti-microbial immune responses, can be co-opted by cancer to evade immune destruction. A plethora of regulatory molecules have been identified. Among them, three have been studied most intensively: cytotoxic T lymphocyte antigen 4 (CTLA4) binding to CD80 or CD86, programmed cell death protein 1 (PD-1) binding to PD-1 ligand 1 (PD-L1) or PD-L2, and SIRPαbinding to CD47. Agents inhibiting CTLA-4, PD1, PD-L1 and CD47 are showing compelling antitumor activity in several solid and hematological cancers. Exploring the role of immune checkpoint pathways in CNSL may help us to establish the rational targeted therapies. In this study, the investigators will investigate the protein expression of several specific molecules in immune checkpoint pathways such as PD-L1, PD-L2 and CD47 in the large neurological resection specimens by immunohistochemical staining of patients with CNSL. Besides, the concentrations of above molecules and other prognostic relevant factors such as chemokine CXCL13, Interleukin-10 and soluble CD19 in the cerebrospinal fluid (CSF) at initial diagnosis and after treatment will be evaluated using enzyme-linked immunosorbent assays. About 100 patients with CNSL will be recruited. The protein expression of the above molecules will be correlated with the clinical outcome of patients with CNSL. The feasibility of adopting these CSF molecules as useful diagnostic or prognostic biomarkers in CNSL will also be investigated.

Conditions

Lymphoma, B-Cell

Outcome Measures

Primary Outcomes (1)

• Overall survival (OS)

  OS was measured from the date of the first diagnosis to the end of the follow-up period, death from any cause, or the date of the last known follow-up examination.

  5 years

Secondary Outcomes (2)

• Progression-free survival (PFS)

  5 years

• Treatment response

  1 year

Interventions

non-intervention OTHER

non-interventional, prospective cohort study

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with newly diagnosed PCNSL at National Taiwan University Hospital from January 1996 to December 2020

You may qualify if:

• \. Patients with newly diagnosed PCNSL at National Taiwan University Hospital from January 1996 to December 2020
• \. Patients aged 20 years and older

You may not qualify if:

• \. Subjects who are involved in any interventional treatment that might change experimental biomarkers, such as PD-L1 inhibitor, PD-1 inhibitor, anti CTLA-4 agents…etc before tumor and CSF sampling.
• \. Pregnancy or breast-feeding

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, 100, Taiwan

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Chieh-Lung Cheng, Dr

  NTUH

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Target Duration: 5 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 15, 2019
• First Posted: November 8, 2019
• Study Start: October 27, 2016
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: January 18, 2023

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)