NCT04532268招募中早期 1 期
Clinical Trial for the Safety and Efficacy of Humanized CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma
Zhejiang University1 个研究点 分布在 1 个国家目标入组 72 人开始时间: 2020年8月23日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 72
- 试验地点
- 1
- 主要终点
- Incidence of treatment-emergent adverse events (TEAEs)
研究概览
简要总结
A Study of Humanized CD19 CAR-T Cells Therapy for Patients With Relapsed and/or Refractory B-cell Acute Lymphoblastic Leukemia and B-cell Non-Hodgkin's Lymphoma.
详细描述
This is a single arm, open-label, single-center study. This study is indicated for relapsed or refractory CD19+ B-cell hematological malignancies, including acute lymphoblastic leukemia and B-cell non-Hodgkin's lymphoma. The selections of dose levels and the numberof subjects are based on clinical trials of similar foreign products. Two groups of patients will be enrolled, 36 in each group. Primary objective is to explore the safety, main consideration is dose-related safety.
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
- 3 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Inclusion criteria only for B-ALL:
- •Male or female aged 3-70 years;
- •Histologically confirmed diagnosis of CD19+ B-ALL per the US National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2016.v1);
- •Relapsed or refractory CD19+ B-ALL (meeting one of the following conditions):
- •CR not achieved after standardized chemotherapy;
- •CR achieved following the first induction, but CR duration is less than 12 months;
- •Ineffectively after first or multiple remedial treatments;
- •2 or more relapses;
- •The number of primordial cells (lymphoblast and prolymphocyte) in bone marrow is >5% (by morphology), and/or >1% (by flow cytometry);
- •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:
- •Male or female aged 18-75 years;
- •Histologically confirmed diagnosis of DLBCL (NOS), FL, DLBCL transformed from CLL/SLL, PMBCL, and HGBCL per the WHO Classification Criteria for Lymphoma (2016);
- •Relapsed or refractory B-NHL (meeting one of the following conditions):
- •No response or relapse after second-line or above chemotherapy regimens;
- •Primary drug resistance;
- •Relapse after auto-HSCT;
- •At least one assessable tumor lesion per Lugano 2014 criteria;
- •Common inclusion criteria for B-ALL and B-NHL:
- •Total bilirubin ≤ 51 umol/L, ALT and AST ≤ 3 times of upper limit of normal, creatinine ≤ 176.8 umol/L;
- •Echocardiogram shows left ventricular ejection fraction (LVEF) ≥ 50%;
- •No active infection in the lungs, blood oxygen saturation in indoor air is ≥ 92%;
- •Estimated survival time ≥ 3 months;
- •ECOG performance status 0 to 2;
- •Patients or their legal guardians volunteer to participate in the study and sign the informed consent.
排除标准
- •Subjects with any of the following exclusion criteria were not eligible for this trial:
- •History of craniocerebral trauma, conscious disturbance, epilepsy, cerebrovascular ischemia, and cerebrovascular hemorrhagic diseases;
- •Electrocardiogram shows prolonged QT interval, severe heart diseases such as severe arrhythmia in the past;
- •Pregnant (or lactating) women;
- •Patients with severe active infections (excluding simple urinary tract infection and bacterial pharyngitis);
- •Active infection of hepatitis B virus or hepatitis C virus;
- •Concurrent therapy with systemic steroids within 2 weeks prior to screening, except for the patients recently or currently receiving inhaled steroids;
- •Previously treated with any CAR-T cell product or other genetically-modified T cell therapies;
- •Creatinine >2.5mg/dl, or ALT / AST>3 times of normal amounts, or bilirubin>2.0 mg/dl;
- •Other uncontrolled diseases that were not suitable for this trial;
- •Patients with HIV infection;
- •Any situations that the investigator believes may increase the risk of patients or interfere with the results of study.
研究组 & 干预措施
Administration of Humanized CD19 CAR T-cells
Experimental
Dose escalation follows the standard 3+3 dose escalation design. A total of 3 dose levels are set for subjects.
干预措施: Humanized CD19 CAR-T cells (Drug)
结局指标
主要结局
Incidence of treatment-emergent adverse events (TEAEs)
时间窗: Up to 2 years after humanized CD19 targeted CAR T-cells infusion
Incidence of treatment-emergent adverse events \[Safety and Tolerability\]
Dose-limiting toxicity (DLT)
时间窗: Baseline up to 28 days after humanized CD19 targeted CAR T-cells infusion
Adverse events assessed according to NCI-CTCAE v5.0 criteria
次要结局
- Quality of life(At Baseline, Month 1, 3, 6, 9 and 12)
- IADL score(At Baseline, Month 1, 3, 6, 9 and 12)
- ADL score(At Baseline, Month 1, 3, 6, 9 and 12)
- HADS score(At Baseline, Month 1, 3, 6, 9 and 12)
- B-cell acute lymphocytic leukemia(B-ALL), Overall response rate (ORR)(At Month 1, 3, 6, 12, 18 and 24)
- B-ALL, Overall survival (OS)(Up to 2 years after humanized CD19 CAR-T cells infusion)
- B-ALL, Event-free survival (EFS)(Up to 2 years after humanized CD19 CAR-T cells infusion)
- B cell non-hodgkin's lymphoma (B-NHL), Overall response rate (ORR)(At Week 4, 12, and Month 6, 12, 18, 24)
- B-NHL, disease control rate (DCR)(At Week 12 and Month 6, 12, 18, 24)
研究者
He Huang
Clinical Professor
Zhejiang University
研究点 (1)
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