NK Cell Therapy for Malignant Solid Brain Tumors

NCT07552233 | Recruiting DMC

• 1 other identifier: 20230484356
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Malignant Solid Brain Tumors; Glioblastoma (GBM); Brain Metastasis; Malignant Meningioma; Glioblastoma Multiforme (GBM)

Keywords

Malignant Solid Brain Tumors; Immunotherapy; Natural Killer Cell; NK Cell

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Objective Response Rate (ORR)

  3 months following NK cells administration

• Duration of response (DOR)

  3 months following NK cells administration

Study Arms (3)

Low dose

EXPERIMENTAL

Intracranial/Intrathecal Injection: 1x10\^8 NK cells, every 2 weeks Intravenous Infusion: 2x10\^8 NK cells, every 2 weeks

Drug: Autologous NK cells

Medium dose

EXPERIMENTAL

Intracranial/Intrathecal Injection: 1x10\^8 NK cells, every 2 weeks Intravenous Infusion: 9x10\^8 NK cells, every 2 weeks

Drug: Autologous NK cells

High dose

EXPERIMENTAL

Intracranial/Intrathecal Injection: 1x10\^8 NK cells, every 2 weeks Intravenous Infusion: 2.9x10\^9 NK cells, every 2 weeks

Drug: Autologous NK cells

Interventions

Autologous NK cells DRUG

Intrathecal Administration Combined with Intravenous Infusion of Autologous NK Cells 1. 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. 2. Intravenous Infusion: Following intracranial/intrathecal injection, the patient receives an intravenous infusion of NK cells.

High dose; Low dose; Medium dose

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, age 18-70 years old (both ends included)
• 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
• Karnofsky Performance Status (KPS) ≥ 60%
• Life expectancy \> 4 weeks, and must be able to undergo an MRI with contrast
• 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)
• Dexamethasone dose ≤ 4 mg/day or equivalent corticosteroid dose, or no dexamethasone administered
• 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

You may not qualify if:

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

Sponsors & Collaborators

• Peking University Third Hospital: lead
• Henan Academy of Innovations in Medical Science: collaborator
• Zhengzhou Second Hospital: collaborator
• Qinhuangdao Runze Hospital: collaborator

Study Sites (4)

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

RECRUITING

Qinhuangdao Runze Hospital

Qinhuangdao, Hebei, 066607, China

NOT YET RECRUITING

Zhengzhou Second Hospital

Zhengzhou, Henan, 450052, China

RECRUITING

Henan Academy of Innovations in Medical Science

Zhengzhou, Henan, 451162, China

RECRUITING

MeSH Terms

Conditions

Glioblastoma; Brain Neoplasms; Meningioma

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 Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neoplasms, Vascular Tissue; Meningeal Neoplasms

Central Study Contacts

Chenlong YANG, M.D., Ph.D.

CONTACT

(+86)-135-1108-7060; vik.yang@pku.edu.cn

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: 3+3 Dose escalation design

Study Record Dates

• First Submitted: April 20, 2026
• First Posted: April 27, 2026
• Study Start: April 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: April 27, 2026

Record last verified: 2026-04

Locations

CN (4)