NK Cell Therapy for Malignant Solid Brain Tumors

NK Cell Therapy for the Treatment of Malignant Solid Brain Tumors

This is a multi-center, open-label investigator-initiated trial (IIT) designed to evaluate the safety, tolerability, and feasibility of combined intracranial and intravenous administration of ex vivo expanded and activated natural killer (NK) cells in adult patients with malignant solid brain tumors who have failed standard treatment modalities. The primary objective is to determine the maximum tolerated dose (MTD) or maximum feasible dose (MFD) of the combined NK cell therapy. Secondary objectives include preliminary assessment of anti-tumor activity as measured by progression-free survival (PFS), overall survival (OS), objective response rate (ORR) per RANO criteria, and evaluation of the immunological effects of NK cell infusion in the tumor microenvironment and peripheral blood.

Study Overview

• Status: Recruiting
• Conditions: Brain Metastasis; Glioblastoma Multiforme (GBM); Glioblastoma (GBM); Malignant Meningioma; Malignant Solid Brain Tumors
• Intervention / Treatment: Drug: Autologous NK cells

• Study Type: Interventional
• Enrollment (Estimated): 27
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chenlong YANG, M.D., Ph.D.; Phone Number: (+86)-135-1108-7060; Email: vik.yang@pku.edu.cn

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100191
      • Recruiting
      • Peking University Third Hospital
      • Contact: Chenlong YANG, M.D., Ph.D.; Phone Number: (+86)-135-1108-7060; Email: vik.yang@pku.edu.cn
  • Hebei
    • Qinhuangdao, Hebei, China, 066607
      • Not yet recruiting
      • Qinhuangdao Runze Hospital
      • Contact: Chenlong YANG, M.D., Ph.D.; Phone Number: (+86)-135-1108-7060; Email: vik.yang@pku.edu.cn
  • Henan
    • Zhengzhou, Henan, China, 450052
      • Recruiting
      • Zhengzhou Second Hospital
      • Contact: Chenlong YANG, M.D., Ph.D.; Phone Number: (+86)-135-1108-7060; Email: vik.yang@pku.edu.cn
    • Zhengzhou, Henan, China, 451162
      • Recruiting
      • Henan Academy of Innovations in Medical Science
      • Contact: Chenlong YANG, M.D., Ph.D.; Phone Number: (+86)-135-1108-7060; Email: vik.yang@pku.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Male or female, age 18-70 years old (both ends included)
2. At least one evaluable lesion with previous biopsy or pathohistologic confirmation of malignant central nervous system tumor, with imaging suggestive of continued progression or recurrence after comprehensive treatment
3. Karnofsky Performance Status (KPS) ≥ 60%
4. Life expectancy > 4 weeks, and must be able to undergo an MRI with contrast
5. Patients who completed radiotherapy or systemic therapies (including temozolomide/bevacizumab or other agents) for at least 4 weeks prior to enrollment. All prior treatment-related toxicities should be defined as ≤ grade 1 (except for toxicities such as alopecia or leukoplakia) according to the Common Terminology Standard for Adverse Events (CTCAE 6.0)
6. Dexamethasone dose ≤ 4 mg/day or equivalent corticosteroid dose, or no dexamethasone administered

7. Must have adequate organ and marrow function as defined below:

   • White blood cell count (WBC) ≥ 3 x 10^9/L
   • Absolute neutrophil count (ANC) > 1 x 10^9/L
   • Hemoglobin (Hb) ≥ 90 g/L
   • Platelet (PLT) ≥ 80×10^9/L
   • Albumin transaminase (ALT) & albumin transaminase (AST) < 1.5 × institutional upper limit of normal (ULN)
   • Serum creatinine (Cr) < 1.5 x institutional ULN
   • Total bilirubin < 1.5 x institutional ULN
   • PT & PTT ≤ 1.25 x institutional ULN
8. No obvious hereditary diseases
9. Normal cardiac function with left ventricular ejection fraction >55%
10. No bleeding and coagulation disorders
11. Absence of positive blood cultures for bacteria, fungus, or virus within 48-hours prior to NK cell infusion and/or there aren't any indications of meningitis
12. Fertile women must have had a pregnancy test with a negative result within 7 days prior to the start of treatment, and subjects are willing to use contraception (hormonal or barrier method of birth control or abstinence) during the clinical trial and for 6 months after the last cell infusion; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
13. Signed, written informed consent

Exclusion Criteria:

1. Active hepatitis B or C virus, HIV infection, or other untreated active infection
2. Pregnant and lactating women
3. Participants with organ failure
4. Participants with a chronic disease requiring immunologic or hormonal therapy
5. Participants with an allergy to immunotherapy and related cells
6. Participants with uncontrolled intercurrent illness
7. Participants with psychiatric illness/social situations that would limit compliance with study requirements
8. Participants with a history of organ transplantation or who are awaiting organ transplantation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose; Intracranial/Intrathecal Injection: 1x10^8 NK cells, every 2 weeks Intravenous Infusion: 2x10^8 NK cells, every 2 weeks	Drug: Autologous NK cells; Intrathecal Administration Combined with Intravenous Infusion of Autologous NK Cells; Intracranial/Intrathecal Injection:NK cells are administered into the cerebrospinal fluid via a surgically implanted intracranial Ommaya reservoir or lumbar puncture. This approach successfully bypasses the blood-brain barrier, allowing NK cells to act directly on tumor lesions in the central nervous system.; Intravenous Infusion: Following intracranial/intrathecal injection, the patient receives an intravenous infusion of NK cells.
Experimental: Medium dose; Intracranial/Intrathecal Injection: 1x10^8 NK cells, every 2 weeks Intravenous Infusion: 9x10^8 NK cells, every 2 weeks	Drug: Autologous NK cells; Intrathecal Administration Combined with Intravenous Infusion of Autologous NK Cells; Intracranial/Intrathecal Injection:NK cells are administered into the cerebrospinal fluid via a surgically implanted intracranial Ommaya reservoir or lumbar puncture. This approach successfully bypasses the blood-brain barrier, allowing NK cells to act directly on tumor lesions in the central nervous system.; Intravenous Infusion: Following intracranial/intrathecal injection, the patient receives an intravenous infusion of NK cells.
Experimental: High dose; Intracranial/Intrathecal Injection: 1x10^8 NK cells, every 2 weeks Intravenous Infusion: 2.9x10^9 NK cells, every 2 weeks	Drug: Autologous NK cells; Intrathecal Administration Combined with Intravenous Infusion of Autologous NK Cells; Intracranial/Intrathecal Injection:NK cells are administered into the cerebrospinal fluid via a surgically implanted intracranial Ommaya reservoir or lumbar puncture. This approach successfully bypasses the blood-brain barrier, allowing NK cells to act directly on tumor lesions in the central nervous system.; Intravenous Infusion: Following intracranial/intrathecal injection, the patient receives an intravenous infusion of NK cells.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs)	Defined as the incidence of ≥ Grade 3-4 adverse events related to NK cells according to common terminology criteria for adverse events (CTCAE) v6.0.	3 months following NK cells administration
Incidence of Dose-Limiting Toxicities (DLTs)	Defined as events attributable to NK cells infusion within 28 days post-infusion. Grade 3 or higher cytokine release syndrome (CRS) lasting more than 2 weeks, according to American Society for Transplantation and Cellular Therapy (ASTCT) criteria; Any NK cells-related AE requiring intubation; Grade 4 non-hematologic toxicities.	28 days following initial treatment with NK cells

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	According to modified RANO criteria, ORR is defined as proportion of subjects with confirmed CR and PR.	3 months following NK cells administration
Duration of response (DOR)	According to modified RANO criteria, DOR is defined as time from the date when a response of confirmed CR/PR is first met to the date of confirmed disease progression or death.	3 months following NK cells administration

Collaborators and Investigators

• Sponsor: Peking University Third Hospital
• Collaborators: Henan Academy of Innovations in Medical Science; Zhengzhou Second Hospital; Qinhuangdao Runze Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: April 20, 2026
• First Submitted That Met QC Criteria: April 20, 2026
• First Posted (Actual): April 27, 2026

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Immunotherapy; NK Cell; Natural Killer Cell; Malignant Solid Brain Tumors
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Nervous System Neoplasms; Neoplasms, Vascular Tissue; Meningeal Neoplasms; Central Nervous System Neoplasms; Glioblastoma; Meningioma; Brain Neoplasms
• Other Study ID Numbers: 20230484356

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No