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.
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
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
Sequential
Autologous NK cells
DrugIntrathecal 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.
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.
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.
Objective Response Rate (ORR)
According to modified RANO criteria, ORR is defined as proportion of subjects with confirmed CR and PR.
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.
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Peking University Third Hospital
Lead sponsor
Henan Academy of Innovations in Medical Science
Collaborator
Zhengzhou Second Hospital
Collaborator
Qinhuangdao Runze Hospital
Collaborator
