GBMdexaB: Function and Composition of Regulatory B Cells in Participants With Glioblastoma

Sponsor

Amsterdam UMC, location VUmc (Other)

Overall Status

Recruiting

CT.gov ID

NCT04128774

Collaborator

(none)

Enrollment

Location

Anticipated Duration (Months)

0.4

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Rationale: This project elaborates on a novel finding of the investigators that has not yet been reported in literature, namely the presence of elevated levels of atypical B cells in participants with glioblastoma. ln the period 2015 2018 the investigators analysed the blood immune subset composition of a cohort of 180 participants undergoing neurosurgery. The most relevant finding was the presence of an abnormally elevated level of B cells in the blood of the great majority of participants with glioblastoma. These B cells may be involved in the immunosuppression associated with glioblastoma that makes this tumor refractory to immunotherapy. Multiple regression analysis indicated that the increase in the frequency of atypical B cells in participants' peripheral blood was related with the administration of dexamethasone prior to surgery. However, this study design did not allow the investigators to address the causality of the relationship between dexamethasone and atypic B cell dysregulation. Alternative treatments to dexamethasone exist.

Objective: To investigate the effect of dexamethasone in the dysregulation of atypic B cells in participants with glioblastoma.

Study design: Observational case control pilot study with 20 participants (10 per group).

Study population: Newly diagnosed participants with glioblastoma. Intervention (if applicable): Observational study. Main study parameters/endpoints: Changes in the immune subset composition and functionality in the peripheral blood of participants with glioblastoma upon administration of dexamethasone for neurological signs of peritumoral edema (oral dexamethasone).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The investigators will collect blood (28 ml) during the first visit and again (28 ml) at the time of surgery (2 weeks ± 3 days). There will not be additional site visits, physical examinations or any other tests, questionnaires. Blood collection is only a minor discomfort and it does not represent any additional risk.

Condition or Disease	Intervention/Treatment	Phase
Glioblastoma, Adult	Drug: Dexamethasone

Study Design

Study Type:

Observational

Anticipated Enrollment :

20 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

The Function and Composition of B Cells in Participants With Glioblastoma Treated With and Without Dexamethasone

Actual Study Start Date :

Jan 1, 2021

Anticipated Primary Completion Date :

Nov 1, 2023

Anticipated Study Completion Date :

Nov 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
GBM-dexa Participants with clinical diagnosis of GBM, that require dexamethasone due to neurological deficits. Dose is based on the clinical judgement of the treating physician but should be given at least two weeks. Dexamethasone is given once a day.	Drug: Dexamethasone The case group receives dexamethasone based on the clinical indication. Other Names: Dexamethasone indicated based on the clinical indication.
GBM-control Participants with clinical diagnosis of GBM not requiring dexamethasone treatment.

Arm

Intervention/Treatment

GBM-dexa

Participants with clinical diagnosis of GBM, that require dexamethasone due to neurological deficits. Dose is based on the clinical judgement of the treating physician but should be given at least two weeks. Dexamethasone is given once a day.

Drug: Dexamethasone

The case group receives dexamethasone based on the clinical indication.

Other Names:

Dexamethasone indicated based on the clinical indication.

GBM-control

Participants with clinical diagnosis of GBM not requiring dexamethasone treatment.

Outcome Measures

Primary Outcome Measures

Frequency of regulatory B cells in blood of participant with Glioblastoma [Two weeks]
ldentify if dexamethasone treatment alters the frequency and functionality of atypic B cells (CD25+CD95Fas+-B cells) in blood in GBM.

Secondary Outcome Measures

Changes in frequency of regulatory B cells after treatment of participants with Glioblastoma with dexamethasone [Two weeks]
Changes in the frequency and functionality of regulatory B cells in blood after two weeks of treatment with dexamethasone.
Changes in frequency of regulatory B cells in participants with Glioblastoma [Two weeks]
Changes in the frequency and functionality of regulatory B cells in blood in patients not treated with dexamethasone.