Optimizing Cytokine-Induced Killer Cells in Glioblastoma Patients

NCT06684899 | Not Yet Recruiting

• 1 other identifier: KillGlio
• Study Type: observational
• Target: 40
• Locations: 0 countries
• Sites: N/A

Brief Summary

The goal of this prospective observational cohort study is to assess the optimal in vitro production protocol for generating Cytokine-Induced Killer (CIK) cells, a type of T lymphocyte, and to evaluate the potential adverse effects of concurrent neuro-oncology therapies on these cells in glioblastoma (GBM) patients. Additionally, the study aims to explore mechanisms to enhance the antitumor activity of CIK cells against GBM by investigating GBM's immune escape mechanisms that may counteract the Human Leukocyte Antigen (HLA)-independent activity of CIK cells. The main questions it aims to answer are: What is the most effective in vitro production protocol for generating highly active CIK cells from GBM patients? Do concurrent chemoradiotherapy or steroid treatments interfere with the activation or efficacy of CIK cells? What are potential strategies to counteract GBM immune escape mechanisms against CIK cells? Researchers will compare CIK cells produced under different protocols, including the use of media supplemented with commercial blood derivatives, to identify the most effective protocol and evaluate the impact of concomitant therapies on CIK cell functionality. Participants will: Undergo a single peripheral blood collection (GBM patients and healthy controls). Have mononuclear cells isolated from their blood samples and expanded in vitro as CIK cells using various production protocols. Have their CIK cells tested in vitro to assess activation status and antitumor activity, identifying optimal production methods and potential strategies to overcome GBM immune escape.

Conditions

Glioblastoma; Cytokine-Induced Killer Cells

Keywords

Glioblastoma; Cytokine-Induced Killer Cells

Outcome Measures

Primary Outcomes (2)

• To optimize the manufacturing process to obtain CIK from patients affected by GBM.

  Cytokine-induced killer cells will be expanded from patients affected by glioblastoma according to different protocols. A statistically significant higher expansion fold compared to the standard (serum-free) protocol will be considered the primary endpoint of Aim 1

  From 3 to 5 weeks after enrollment

• To establish the best applicability conditions of CIK in patients affected by GBM.

  Cytokine-induced killer (CIK) cells will be treated with sequential doses of dexamethasone and temozolomide. The determination of the median toxic dose (TD50) will be considered as the endpoint to explore the concomitant use of these therapies.

  From 3 to 5 weeks after enrollment

Study Arms (2)

Patients affected by glioblastoma

Subject with a documented diagnosis of glioblastoma (WHO criteria 2021), as confirmed by reference histopathology at San Raffaele Hospital.

Healthy controls

Healthy donors will also be enrolled in the study to serve as controls in the manufacturing process and exploratory analysis. They will be recruited among healthy individuals attending our Unit

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

We will screen the patients affected by glioblastoma, diagnosed at the San Raffaele Hospital according to the World Health Organization criteria 2021. Patients fulfilling the inclusion and exclusion criteria will be enrolled and a blood sample will be obtained in the window period between the diagnosis (biopsy or tumor debulking) and the start of the standard radio-chemotherapy regimen. Both male and female patients will be enrolled to obtain, if possible, equal representation in the analysis. Healthy donors will also be enrolled in the study to serve as controls in the manufacturing process and exploratory analysis.

You may qualify if:

• Age ≥18 years.
• Subject is willing and able to provide informed consent for participation in the study.
• Subject with a documented diagnosis of GBM (WHO criteria 2021), as confirmed by reference histopathology at San Raffaele Hospital.
• Age ≥18 years.
• Subject is willing and able to provide informed consent for participation in the study.
• Subjects In good general health as evidenced by medical history

You may not qualify if:

• Subject is not willing or able to provide informed consent for participation in the study. - Pregnancy
• Presence of an acute infection requiring active treatment.
• Documented ematological abnormalities: leukocytes \< 3,000/μl or lymphocytes \< 500/μl or neutrophils \< 1,000/μl or hemoglobin \< 9 g/100 ml or thrombocytes \< 100,000/μl, based on the most recent laboratory tests performed for clinical practice.
• Documented immune deficiency
• Documented autoimmune disease.
• Documented positive serology for HIV or HBs antigen.

Sponsors & Collaborators

• IRCCS San Raffaele: lead

MeSH Terms

Conditions

Glioblastoma

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Central Study Contacts

Giacomo Sferruzza, MD

CONTACT

+393514190013; sferruzza.giacomo@hsr.it

Gaetano Finocchiaro, MD

CONTACT

+39022643-2878; finocchiaro.gaetano@hsr.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 11, 2024
• First Posted: November 12, 2024
• Study Start: November 1, 2024
• Primary Completion: November 1, 2024
• Study Completion: November 1, 2024
• Last Updated: November 14, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share