NCT06751134招募中1 期
A Study to Evaluate the Safety, Preliminary Efficacy, Pharmacokinetics of CNK-UT Cells to Treat the Patients with Relapsed/refractory Neuroblastoma
Nanjing Children's Hospital2 个研究点 分布在 1 个国家目标入组 12 人开始时间: 2024年12月28日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 12
- 试验地点
- 2
- 主要终点
- Incidence of Treatment Related adverse events (AEs)
研究概览
简要总结
This is a single arm, open-label, multi-center, pilot studies (Investigator Initiated Trial, IIT) to evaluate the safety, preliminary efficacy, pharmacokinetics of universal T-cells engineered with chimeric natural killer receptor (CNK-UT) to treat the patients with relapsed/refractory Neuroblastoma.
详细描述
This is a single arm, open-label, phase I, dose escalation/dose expansion study to assess the safety of CNK-UT cells therapy, and to obtain the preliminary efficacy and pharmacokinetics result in participants who have been diagnosed with relapsed/refractory Neuroblastoma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 12 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 1-12 years with weight≥10kg, male or female;
- •The child and/or guardian has signed the informed consent form (ICF) and has the ability to comply with the study requirements.
- •Diagnosed with relapsed/refractory neuroblastoma. Clinical diagnostic criteria and first-line standard treatment can refer to the NCCN guidelines:
- •Relapsed neuroblastoma: New lesions appear at the primary site or other locations 4 weeks after achieving complete remission through first-line standard treatment.
- •Refractory neuroblastoma: Failure to achieve complete remission after standard treatment protocols, which include induction chemotherapy, surgery, and radiotherapy targeting the primary tumor and residual metastatic sites;
- •Prior to enrollment, appropriate measures can be implemented to ensure that the subject's disease status is either partial remission (PR) or stable disease (SD).
- •According to the INRC efficacy criteria, there must be at least one lesion whose efficacy can be assessed through functional imaging (123I-MIBG) and/or bone marrow examination (bone marrow aspiration or biopsy). If soft tissue lesions are present, the longest diameter of the target lesion should be ≤2 cm.
- •Tumor tissue sections or paraffin blocks can be provided, and it has been confirmed through immunohistochemistry (IHC) that the tumor tissue expresses B7-H
- •Lansky score>60；
- •Estimated life expectancy > 12 weeks;
- •Adequate organ and bone marrow function, and the laboratory test value meets the following requirements within 7 days before enrollment, as follows:
- •(1)Blood Routine Test: Absolute neutrophil count(ANC)≥1.5×10^9/L;Absolute lymphocyte count (ALC)≥0.2×10^9/L；Platelet count ≥75×10^9/L; Haemoglobin≥90g/L; (2)Heart: Left ventricular ejection fraction (LVEF)≥50%;Cardiac function Grade I-II; (3)Pulmonary function: indoor oxygen saturation≥92%. (4)Hepatic function：Total bilirubin≤3×ULN; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT)≤5×ULN; (5)Renal function: Serum creatinine≤2×ULN, or Creatinine clearance rate (CCR)≥60 mL/min (Cockroft-Gault formula); 10.All toxic responses originating from previous radiotherapy, chemotherapy, or other treatments (occurring within 4 weeks or 5 half-lives of anti-tumor drugs therapy [including but not limited to chemotherapy, targeted therapy, immunotherapy, Chinese herbal medicine]) have returned to NCI CTCAEV5.0 Grade≤1 (except for hair loss).
排除标准
- •Suffering from malignant tumors or diagnosed within 5 years before enrollment, excluding radical skin basal cell carcinoma, skin squamous cell carcinoma, thyroid cancer, breast cancer (ductal carcinoma in situ) and / or radical resection of carcinoma in situ.
- •Participants with symptomatic central nervous system (CNS) metastasis confirmed by imaging or pathological examination.
- •Participants with MIBG non-avid disease.
- •Participants with a history of organ transplantation（excluding stem cell transplantation）;
- •Participants with active autoimmune diseases requiring systemic treatment (such as the use of disease-modifying drugs, corticosteroids, or immunosuppressants) are considered. The use of replacement therapies (such as thyroxine, insulin, or physiological corticosteroids for adrenal or pituitary insufficiency) is permitted. A known history of primary immunodeficiency is also noted. For patients who only test positive for autoimmune antibodies, the presence of autoimmune disease must be confirmed based on the investigator's judgment.
- •Uncontrolled or irreparable systemic diseases, metabolic disorders, or other non-malignant organ diseases or cancer sequelae, which may lead to higher medical risks and/or uncertainties in survival assessment.
- •Active pulmonary tuberculosis (TB), who is receiving anti-tuberculosis treatment or has received anti-tuberculosis treatment within 1 year before enrollment; human immunodeficiency virus (HIV) infection, known syphilis infection.
- •Severe infections that are either active or poorly controlled clinically within 4 weeks prior to enrollment, including but not limited to hospitalization due to infections, bacteremia, or severe pneumonia complications (excluding mild urinary tract infections and upper respiratory tract infections).
- •Received radiotherapy, chemotherapy (excluding lymphodepletion), molecular targeted therapy, immune checkpoint inhibitors, or other anti-tumor treatments within 4 weeks or 5 half-lives (whichever is shorter) before cell infusion..
- •Participants who have undergone major surgery (craniotomy, thoracotomy, or laparotomy) within 4 weeks prior to the initiation of the study, or have severe unhealed wounds, ulcers, or fractures.
- •Participants who have received treatment from other clinical trials within 4 weeks prior to the initiation of the study.
- •Participants who receive attenuated live vaccines within 4 weeks prior to the initiation of the study.
- •Participants who have used any gene therapy products prior to cell infusion.
- •Allergic to components of CNK-UT injection.
- •Participants suffer from known mental or substance abuse disorders, which may interfere with their ability to comply with research requirements.
- •Participants considered by the investigator to have other potentially life-threatening serious complications that may interfere with the evaluation of this study..
- •Other situations that the participant is identified by the investigator as unsuitable to participate in the study.
研究组 & 干预措施
CNK-UT cells therapy
Experimental
- Dose Escalation： Single-dose intravenous injection of CNK-UT cells (3~34×10^7 CNK+ cells/kg).
- Dose Expansion:
Multiple-dose intravenous injection of CNK-UT cells according to the results of dose escalation.
干预措施: Chimeric Natural Killer Receptor Universal T-cells (CNK-UT) (Drug)
结局指标
主要结局
Incidence of Treatment Related adverse events (AEs)
时间窗: up to 1 year
Incidence of Treatment Related AEs, AEs of special interest and serious adverse events (SAEs) assessed by NCI-CTCAE v5.0 criteria
次要结局
- Objective Response Rate (ORR)(up to 1 year)
- Duration of Response (DOR)(up to 1 year)
- Disease control rate (DCR)(up to 1 year)
- Progression-free Survival (PFS)(up to 1 year)
- Overall survival (OS)(up to 1 year)
- Pharmacokinetics (PK) (Cmax)(up to 1 year)
- Pharmacokinetics (PK) (Tmax)(up to 1 year)
研究者
Fang Yongjun
Prof.
Nanjing Medical University
研究点 (2)
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