A Multicenter, Open-label, Externally Controlled Clinical Study to Evaluate the Safety and Efficacy of Autologous Natural Killer Cell (CHANK-101) in Patients With Recurrent Glioblastoma
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- Progression-Free Survival (PFS)
研究概览
简要总结
This multicenter, open-label, externally controlled clinical study is designed to evaluate the safety and efficacy of CHANK-101, an autologous natural killer (NK) cell therapy, in patients with recurrent glioblastoma. The primary objective is to evaluate progression-free survival (PFS) following CHANK-101 administration. Secondary objectives include evaluating safety and tolerability, progression-free survival at 6 months (PFS-6), and overall survival (OS).
详细描述
This is a multicenter, open-label, externally controlled exploratory clinical study evaluating the safety and efficacy of CHANK-101, an autologous natural killer (NK) cell therapy, in patients with recurrent glioblastoma. The study is intended to assess the feasibility and safety of CHANK-101 administration and to explore signals of clinical efficacy to inform the design of future confirmatory studies. Eligible participants will undergo leukapheresis for the collection of peripheral blood cells used for the manufacture of CHANK-101. The first intravenous administration of CHANK-101 will begin 4 to 6 weeks after leukapheresis. For participants scheduled to undergo surgical resection of the recurrent lesion, leukapheresis will be performed within 2 weeks before surgery, and the first administration of CHANK-101 will begin 4 to 6 weeks after surgery. CHANK-101 will subsequently be administered intravenously every 2 weeks for up to 12 administrations. The primary efficacy endpoint is progression-free survival (PFS), assessed according to the Response Assessment in Neuro-Oncology (RANO) 2.0 criteria. Secondary evaluations include the safety and tolerability of CHANK-101, progression-free survival at 6 months (PFS-6), and overall survival (OS). Because of the challenges associated with establishing a randomized control group in this patient population, clinical outcomes in participants receiving CHANK-101 will be compared with those of an external control group. The external control group will consist of patients from the same participating institutions and will be evaluated using the same eligibility criteria and assessment criteria as the CHANK-101 treatment group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female adults aged 19 years to less than 70 years who have received sufficient explanation regarding the purpose, methods, potential benefits, and risks of the study and have voluntarily provided written informed consent.
- •Histologically confirmed IDH-wildtype glioblastoma (GBM), WHO Grade 4, according to the WHO CNS5 2021 classification.
- •Completion of standard first-line treatment (surgery + radiotherapy + concurrent TMZ → 6 cycles of adjuvant TMZ).
- •Confirmed first recurrence, defined by at least one of the following:
- •(1) Progressive Disease according to RANO 2.0 criteria on MRI more than 12 weeks after completion of radiotherapy.
- •(2) If within 12 weeks after completion of radiotherapy, pseudoprogression has been excluded through the RANO 2.0 confirmation procedure (confirmatory scan), and persistent progression has been confirmed on two consecutive scans at least 4 weeks apart.
- •5. No antitumor treatment, including chemotherapy, immunotherapy, targeted therapy, or radiotherapy, after confirmation of recurrence, except surgery.
- •7. Adequate organ function permitting study treatment and surgery, including:
- •Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L.
- •Platelets ≥ 100 × 10^9/L.
- •Hemoglobin (Hb) ≥ 9.0 g/dL.
- •AST and ALT ≤ 2.5 × ULN.
- •Total bilirubin ≤ 1.5 × ULN.
- •Serum creatinine ≤ 1.5 × ULN or eGFR ≥ 50 mL/min/1.73 m^
- •8. Adequate peripheral venous access for leukapheresis or ability to undergo central venous catheter placement.
- •9. Life expectancy of at least 12 weeks, as determined by the investigator.
- •10. Female participants who are postmenopausal, defined as 12 months of amenorrhea without a medical cause, or women of childbearing potential with a negative pregnancy test.
- •11. Women of childbearing potential and male participants who agree to use appropriate contraception (e.g., condoms, hormonal contraceptives, oral contraceptives, intrauterine devices, or sterilization) during the study and for 3 months after the last administration of the study treatment.
排除标准
- •Two or more recurrences or prior antitumor treatment for a previous recurrence.
- •Confirmed leptomeningeal dissemination or extracranial metastasis.
- •Requirement for chronic high-dose systemic corticosteroids (e.g., >10 mg/day prednisolone equivalent) or continuous use of other immunosuppressive drugs. Low-dose corticosteroid use at enrollment is permitted; however, the washout criteria must be met at each study treatment administration.
- •Active autoimmune disease requiring systemic immunosuppressive treatment within the past 2 years (e.g., steroids ≥10 mg/day prednisolone equivalent or immunosuppressive agents). Exceptions include adequately treated Basedow/Graves disease or Hashimoto thyroiditis with stable thyroid hormone replacement therapy, vitiligo, resolved childhood asthma, type 1 diabetes, and localized skin disorders.
- •A positive result for any of the following infectious disease tests performed at screening. However, participants with a positive result may participate if the investigator determines that it has no clinically significant impact on participation in the study:
- •(1) HBsAg/HBV NAT. (2) HCV Ab/HCV NAT. (3) HIV Ab/HIV NAT. (4) Syphilis (non-treponemal/treponemal). (5) HTLV Ab. (6) CMV Ab/CMV NAT.
- •6. Uncontrolled active infection or any other infectious disease considered by the investigator to be inappropriate for participation in the study.
- •7. History of another malignancy within the past 3 years, except adequately treated basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ.
- •8. Contraindication to leukapheresis (e.g., severe cardiovascular disease or coagulation disorder).
- •9. Serious medical or psychiatric condition that may affect participation in the study.
- •10. History of a severe allergic reaction or other serious hypersensitivity to the study treatment or any of its excipients.
- •11. Pregnant or breastfeeding women.
- •12. Participants planning pregnancy during the study.
- •13. Participants considered by the investigator unlikely to comply with study treatment, study procedures, or follow-up.
- •14. Any other participant considered by the investigator to be unsuitable for participation in the study.
研究组 & 干预措施
CHANK-101 Treatment Group
Participants will receive CHANK-101, an autologous natural killer (NK) cell therapy, by intravenous administration. The first administration will begin 4 to 6 weeks after leukapheresis, or 4 to 6 weeks after surgery for participants undergoing surgical resection of the recurrent lesion. CHANK-101 will subsequently be administered every 2 weeks for up to 12 administrations.
干预措施: CHANK-101 (Biological)
结局指标
主要结局
Progression-Free Survival (PFS)
时间窗: From the first administration of CHANK-101 until disease progression or death from any cause, whichever occurs first, assessed up to Week 48.
Progression-free survival (PFS) is defined as the time from the first administration of CHANK-101 to the first occurrence of disease progression according to RANO 2.0 criteria or death from any cause, whichever occurs first.
次要结局
- Number of Participants With Adverse Events as Assessed by NCI-CTCAE Version 5.0(From the first administration of CHANK-101 through Week 48.)
- Progression-Free Survival at 6 Months (PFS-6)(6 months after the first administration of CHANK-101)
- Overall Survival (OS)(From the first administration of CHANK-101 until death from any cause, assessed up to Week 48.)
研究者
KYOUNGSU SUNG
Associate Professor
Dong-A University Hospital