肿瘤细胞治疗研究
英文原题：A Study of Murine CD19 CAR-T Therapy for Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancies
⚠ 该试验的登记信息已有 72 个月未更新， 页面上显示的「招募中」可能已经失效。联系研究中心之前，建议先到 ClinicalTrials.gov 核对登记原文的最新状态与联系方式。
这是一项早期 I 期注册临床试验，评估 CD19CAR-T 细胞治疗急性淋巴细胞白血病、非霍奇金淋巴瘤的安全性、可行性及初步疗效。当前状态：招募中。计划入组 120 例。试验地点：中国 · 杭州（共 1 个中心，其中中国 1 个）。登记号：NCT04532281。
不限性别
纳入标准： 仅适用于B-ALL： 1. 根据美国国家综合癌症网络（NCCN）急性淋巴细胞白血病临床实践指南（2016.v1），组织学确诊为CD19阳性B-ALL。 2. 复发／难治性CD19阳性B-ALL，符合以下任一情况：标准化疗后未达到完全缓解（CR）；首次诱导治疗后达到CR但持续时间<12个月；首次或多次挽救治疗无效；复发≥2次。 3. 骨髓原始细胞（淋巴母细胞和前淋巴细胞）比例>5%（形态学）和／或>1%（流式细胞术）。 4. 费城染色体阴性（Ph−），或Ph+但不能耐受TKI治疗或对2种TKI治疗无应答。 仅适用于B-NHL： 1. 根据WHO 2016年淋巴瘤分类标准，组织学确诊为DLBCL（NOS）、滤泡性淋巴瘤（FL）、由CLL/SLL转化的DLBCL、原发纵隔大B细胞淋巴瘤（PMBCL）或高级别B细胞淋巴瘤（HGBCL）。 2. 复发／难治性B-NHL，符合以下任一情况：二线及以上化疗方案治疗后无应答或复发；原发耐药；自体造血干细胞移植（auto-HSCT）后复发。 3. 根据2014年Lugano标准至少有1个可评估肿瘤病灶。 B-ALL和B-NHL共同纳入标准： 1. 总胆红素≤51 μmol/L，ALT和AST≤ULN的3倍，肌酐≤176.8 μmol/L。 2. 超声心动图显示左心室射血分数（LVEF）≥50%。 3. 肺部无活动性感染，室内空气下血氧饱和度≥92%。 4. 预期生存期≥3个月。 5. ECOG体能状态评分0～2分。 6. 患者或其法定监护人自愿参加研究并签署知情同意书。 排除标准： 符合以下任一排除标准者不得参加： 1. 有颅脑外伤、意识障碍、癫痫、脑血管缺血或脑出血性疾病史。 2. 心电图显示QT间期延长，或既往患有严重心脏病（如严重心律失常）。 3. 妊娠或哺乳期女性。 4. 存在严重活动性感染（单纯尿路感染和细菌性咽炎除外）。 5. 乙型肝炎病毒或丙型肝炎病毒活动性感染。 6. 筛选前2周内同时接受全身类固醇治疗；近期或目前接受吸入性类固醇治疗者除外。 7. 既往接受过任何CAR-T产品或其他基因修饰T细胞治疗。 8. 肌酐>2.5 mg/dL，或ALT/AST>正常值的3倍，或胆红素>2.0 mg/dL。 9. 存在不适合参加本试验的其他未控制疾病。 10. HIV感染。 11. 研究者认为可能增加患者风险或干扰研究结果的任何情况。
Inclusion Criteria:
* Inclusion criteria only for B-ALL:
1. Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1)；
2. Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):
1. CR not achieved after standardized chemotherapy;
2. CR achieved following the first induction, but CR duration is less than 12 months;
3. Ineffectively after first or multiple remedial treatments;
4. 2 or more relapses;
3. The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is \> 5% (by morphology), and/or \> 1% (by flow cytometry);
4. Philadelphia-chromosome-negative (Ph-) patients; or Philadelphia-chromosome-positive (Ph+) patients who cannot tolerate TKI treatments or do not respond to 2 TKI treatments;
* Inclusion criteria only for B-NHL:
1. Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016);
2. Relapsed or refractory B-NHL (meeting one of the following conditions):
1. No response or relapse after second-line or above chemotherapy regimens;
2. Primary drug resistance;
3. Relapse after auto-HSCT;
3. At least one assessable tumor lesion per Lugano 2014 criteria;
* Common inclusion criteria for B-ALL and B-NHL:
1. Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;
2. Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
3. No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;
4. Estimated survival time ≥ 3 months;
5. ECOG performance status 0 to 2;
6. Patients or their legal guardians volunteer to participate in the study and sign the informed consent.
Exclusion Criteria:
Subjects with any of the following exclusion criteria were not eligible for this trial:
1. History of craniocerebral trauma, conscious disturbance, epilepsy,cerebrovascular ischemia, and cerebrovascular, hemorrhagic diseases;
2. Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
3. Pregnant (or lactating) women;
4. Patients with severe active infections (excluding simple urinary tractinfectionand bacterial pharyngitis);
5. Active infection of hepatitis B virus or hepatitis C virus;
6. Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving in haled steroids;
7. Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
8. Creatinine\>2.5mg/dl, or ALT / AST \> 3 times of normal amounts, or bilirubin\>2.0 mg/dl;
9. Other uncontrolled diseases that were not suitable for this trial;
10. Patients with HIV infection;
11. Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.以上为辅助阅读译文。是否适合入组须由主治医生判断，最终以登记平台与研究者确认为准。
主要终点：Dose-limiting toxicity (DLT) · Adverse events assessed according to NCI-CTCAE v5.0 criteria · Baseline up to 28 days after murine CD19 targeted CAR T-cells infusion；Incidence of treatment-emergent adverse events (TEAEs) · Incidence of treatment-emergent adverse events \[Safety and Tolerability\] · Up to 2 years after murine CD19 targeted CAR T-cells infusion
次要终点：B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR)；B-ALL, Overall survival (OS)；B-ALL, Event-free survival (EFS)；B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)；B-NHL, disease control rate (DCR)；Quality of life；Activities of Daily Living (ADL) score；Instrumental Activities of Daily Living (IADL) score
一项研究，评估小鼠源CD19 CAR-T细胞治疗复发或难治性CD19阳性B细胞血液系统恶性肿瘤患者。
A Study of Murine CD19 CAR-T Cells Therapy for Patients With Relapsed or Refractory CD19+ B-cell Hematological Malignancies.
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