Phase 1/2 Trial Integrating Allogeneic NK Cells in High-risk Advanced Stage III-IV Nasopharyngeal Cancer Patients
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 31
- 主要终点
- The percentage of patients with detectable plasma EBV-DNA decreased to 10% post treatment
研究概览
简要总结
This clinical trial aims to determine whether Natural Killer (NK) cell therapy administered in combination with concurrent chemoradiotherapy (CRT) can reduce recurrence in patients with advanced nasopharyngeal cancer (NPC), and to identify the highest safe and tolerable dose of allogeneic NK cells. Allogeneic NK cells, derived from healthy donors, have demonstrated good tolerability in cancer patients.
The primary research questions are:
- What is the maximum tolerated dose (MTD) of allogeneic NK cells when administered with CRT in NPC patients?
- Can the addition of allogeneic NK cells to standard CRT reduce the proportion of NPC patients with detectable plasma EBV-DNA from 30% to 10%?
Phase 1: Participants will receive one of five escalating doses of allogeneic NK cells with CRT to determine the MTD.
Phase 2: Participants will receive the established MTD NK dose together with CRT.
Participants will undergo regular safety monitoring, side-effect assessment, measurement of plasma EBV-DNA levels, and surveillance for disease recurrence.
详细描述
The investigator plans to enrol 31 newly diagnosed NPC patients with Stage III-IVA/B (T1-4, N1-3, M0) disease who are scheduled to receive standard-of-care treatment over an estimated 24-36-month period.
The clinical trial consists of a Phase 1 dose-escalation study followed by a single-arm Phase 2 study. In Phase 1, at least six participants will be treated at the MTD of allogeneic NK cells, after which an additional 25 participants are expected to be enrolled in Phase 2.
Phase 1 will use the Bayesian Model Averaging Continual Reassessment Method (BMA-CRM) to determine the MTD, evaluating five NK-cell dose levels of 0.5×10⁷, 0.8×10⁷, 1.1×10⁷, 1.4×10⁷, and 1.8×10⁷ cells/kg, with the starting dose set at 0.8×10⁷ cells/kg. Dose-limiting toxicity (DLT) is defined as Grade 3 to 5 toxicities per CTCAE criteria, and the target toxicity limit (TTL) is set at a maximum allowable DLT probability of 30%. Toxicity probability will be reassessed whenever a DLT occurs to determine whether it exceeds the TTL. If the cohort completes evaluation at a given dose level and the toxicity probability is within the TTL, dose escalation will proceed; however, if the toxicity probability exceeds the TTL, the dose will be rejected, and de-escalation will occur. When toxicity probability is low, accelerated escalation may be implemented.
Phase 1 will conclude once six participants have been treated at the designated MTD without developing Grade 3 to 5 toxicities; at that point, the MTD will be accepted. All participants in Phase 1 will receive standard NPC treatment combined with the NK-cell dose evaluated at the time of their enrollment.
Phase 2 is a single-arm study based on historical findings that approximately 25% to 30% of locally advanced NPC patients continue to exhibit detectable circulating EBV-DNA following standard CRT. The study hypothesizes that the addition of allogeneic NK cells will reduce this proportion to 10%.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 21 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosed with NPC Stage III-IVA/B (T1-4, N1-3, M0)
- •Able to tolerate convectional CRT
- •Detectable EBV level at diagnosis
- •Adequate organ function ANC ≥ 1500/µL Platelet count ≥ 100,000/µL Creatinine clearance ≥60ml/minute Total bilirubin ≤ 1.5 x upper limit normal (ULN) AST ≤ 2 x upper limit normal ALT ≤ 2 x upper limit normal
- •ECOG performance status of 0-1
排除标准
- •History of Autoimmune Disease or any condition resulting in immunocompromised state (e.g., Drug induced)
- •ECOG performance status above or equal to 2
- •Poor Organ Function
- •Lactating or pregnant
- •Serious concomitant disorders that would compromise the safety of the patient or compromise the patient's ability to complete the study.
研究组 & 干预措施
Concurrent and adjuvant allogeneic NK cell therapy
Participants will receive standard chemoradiotherapy for locally advanced nasopharyngeal carcinoma along with adjuvant therapy of NK cells. Nk cells would be enriched and expanded using PBMCs from healthy donors.
Phase 1 dose escalation study which uses 5 different dosages of 0.5 x 10^7, 0.8x10^7, 1.1x10^7, 1.4 x 10^7, and 1.8x10^7 to determine the Maximum tolerated dose (MTD). If the MTD is determined in phase 1, the study will enter phase 2, where the determined dose level will be used for participants. The participants will receive six intravenous NK cell infusions at weeks 3,6,7,8,9, and 10 during and after CRT. If the participant's EBV level is still detectable, they would be suggested for supplementary NK cell treatments for an additional four weeks.
干预措施: Allogenic expanded Natural Killer Cells (AlloNK1) (Biological)
结局指标
主要结局
The percentage of patients with detectable plasma EBV-DNA decreased to 10% post treatment
时间窗: From day of enrollment to the end of treatment at week 10
Primary endpoint is set at the percentage of patients with detectable post-treatment circulating EBV-DNA has decreased from 30% to 10%.
Determine the MTD of allogenic NK cells
时间窗: From enrollment to the end of treatment at week 10
The primary objective of this trial is to determine the MTD of allogeneic NK cells when used with concurrent CRT in advanced NPC patients.
次要结局
- Determine the patient survival and recurrence rate post-treatment(24 to 36 months after the last treatment done at week 10)