Injection of Active Allogeneic Natural Killer Cells in Patients With Gliomas

Efficacy of the Intrathecal Injection of Active Allogeneic Natural Killer Cells in Patients With High-grade Gliomas; A Multi-center Phase II Clinical Trial

Gliomas are the most common malignant brain tumors, which are often associated with high-grade tumors characterized by an inferior prognosis and low patient survival rates in both children and adults. Surgical removal and tumor resection are the primary treatment approaches for gliomas. In such cases, whole-brain radiation therapy is also employed as a therapeutic option, which itself has significant side effects, and studies have shown limited impact on improving patient survival. Targeted therapy and recently investigated approaches such as targeted therapy have shown some tumor regression, but in most cases, tumor recurrence has been observed after initial regression. Therefore, they have a limited impact on prolonging patient survival. Immunotherapy, particularly immunotherapy with specific immune cells, can effectively identify and eliminate cancer cells and has been utilized as a new approach in the past two decades, especially in cancers where conventional methods have limited success. Among the effective immunotherapy methods, using natural killer cells (NK cells) can be one of the promising approaches. Currently, phase I clinical trials have been conducted by our research group in patients with gliomas.

Study Overview

• Status: Recruiting
• Conditions: Glioma Glioblastoma Multiforme; High Grade Glioma (III or IV)
• Intervention / Treatment: Biological: NK cell therapy

Detailed Description

Inclusion criteria:

New diagnosed patients with grade 3 or 4 brain tumor, based on WHO classification, which are included in the one of the following conditions: • Astrocytoma, IDHmutant • Oligodendroglioma, IDH-mutant • Glioblastoma, IDH-wild type • Diffuse midline glioma • Diffuse hemispheric glioma • Diffuse pediatric-type high-grade glioma, IDH-wild type Age range of 3 to 60 years old both sex Lansky/Karnofsky performance score above 60 Obtained informed consent of patients or parents or legal attendance in cases of pediatrics Hemoglobin above 10 gr/dL of blood Absolute granulocyte count (AGC) above 500 per microliter of blood Platelet count above 50000 per microliter of blood INR below 2 and PTT less than 1.5 times of maximum normal value Plasma bilirubin level less than 1.5 times of maximum normal value Plasma hepatic transaminases (ALT and AST) level less than 3 times of maximum normal value Plasma creatinine level less than 1.5 times of maximum normal value

Exclusion criteria:

Evidence of radio necrosis in MRI or MRS Intolerance of new treatment due to emergency condition History of other malignancies History of any immunodeficiency diseases or any immune compromising conditions Rupture of cerebral shunt or unable to perform a lumbar puncture Pregnancy History of uncontrolled chronic diseases such as: Diabetes, CHF, liver cirrhosis, CKD, etc

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Marzieh Ebrahimi, PhD; Phone Number: +98 21 235 62516; Email: mebrahimi@royan-rc.ac.ir
• Study Contact Backup: Name: Mohammad Faranoush, MD; Phone Number: +98 9121590517

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of, 1343864331
    • Recruiting
    • Rasoul Akram Hospital
    • Contact: Mohammad Faranoush, MD; Phone Number: +98 9121590517; Email: faranoush.m@iums.ac.ir

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: New diagnosed patients with grade 3 or 4 brain tumor, based on WHO classification, which are included in the one of the following conditions: • Astrocytoma, IDHmutant • Oligodendroglioma, IDH-mutant • Glioblastoma, IDH-wild type • Diffuse midline glioma • Diffuse hemispheric glioma • Diffuse pediatric-type high-grade glioma, IDH-wild type Age range of 3 to 60 years old both sex Lansky/Karnofsky performance score above 60 Obtained informed consent of patients or parents or legal attendance in cases of pediatrics Hemoglobin above 10 gr/dL of blood Absolute granulocyte count (AGC) above 500 per microliter of blood Platelet count above 50000 per microliter of blood INR below 2 and PTT less than 1.5 times of maximum normal value Plasma bilirubin level less than 1.5 times of maximum normal value Plasma hepatic transaminases (ALT and AST) level less than 3 times of maximum normal value Plasma creatinine level less than 1.5 times of maximum normal value -

Exclusion Criteria: Evidence of radio necrosis in MRI or MRS Intolerance of new treatment due to emergency condition History of other malignancies History of any immunodeficiency diseases or any immune compromising conditions Rupture of cerebral shunt or unable to perform a lumbar puncture Pregnancy History of uncontrolled chronic diseases such as: Diabetes, CHF, liver cirrhosis, CKD, etc

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Test group; patients will recieve 3 cources of 2* 10 8 intrathecal infusion of NK cells every 3 weeks	Biological: NK cell therapy; Active NK cell injection through lumbar puncture in patient with Astrocytoma IDH-mutant, Oligodendroglioma IDHmutant, Glioblastoma IDH-wild type, Diffuse midline glioma, Diffuse hemispheric glioma, Diffuse pediatrictype high-grade glioma IDH-wild type
No Intervention: Control group; patients will recieve only conventional treatment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To measure tumor response after infusion of intrathecal NK cells	Imaging and Immunotherapy Response Assessment in Neuro-oncology (iRANO) guidelines	From enrollment to the end of treatment at 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events (AEs)	Using CTCAEs (Common Terminology Criteria for Adverse Events) checklist	From enrollment to the end of treatment at one months

Collaborators and Investigators

• Sponsor: Marzieh Ebrahimi

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2024
• Primary Completion (Estimated): November 25, 2025
• Study Completion (Estimated): November 25, 2027

Study Registration Dates

• First Submitted: November 12, 2024
• First Submitted That Met QC Criteria: November 12, 2024
• First Posted (Actual): November 13, 2024

Study Record Updates

• Last Update Posted (Actual): April 9, 2025
• Last Update Submitted That Met QC Criteria: April 5, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: glioblastoma; natural killer cells; NK cells; high grade gliomas; Brain glioma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Glioma
• Other Study ID Numbers: IR.ACECR.ROYAN.REC.1402.001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No