Clinical Study of Universal Off-the-shelf Cell Products in Patients With CD19-positive Relapsed/Refractory B-cell Hematolymphatic Malignancies.
试验速览
- 阶段
- 早期 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Assessment of the safety after UTAA09 injection treatment
研究概览
简要总结
This study is designed for exploring the preliminary safety and efficacy of the recombinant allogeneic healthy γδT cells transduced with the anti-CD19 lentiviral vector in patients with CD19-positive B cell hematolymphatic malignancies.
详细描述
A single arm open-label clinical study is designed to prelinarily determine the safety, efficacy, the ratio of CD19-positive cells in peripheral blood and cell kinetics after administration of UTAA09 injection in patients with CD19-positive relapsed/refractory B-cell hematolymphatic malignancies. All subjects will receive UTAA09 cells infusion.
Primary objective: explore the preliminary safety and efficacy of UTAA09 injection in patients with CD19-positive relapsed/refractory B-cell line hematolymphatic malignancies.
Secondary objectives:
- explore the distribution, amplification and survival of UTAA09 cells in vivo after administration of UTAA09 injection;
- explore the ratio of CD19-positive cells in peripheral blood after administration of UTAA09 injection.
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 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients aged between 3~70 (including cut-off values), regardless of gender and race;
- •Expected survival time>12 weeks;
- •ECOG score 0-2;
- •CD19-positive relapsed/refractory B-cell hematolymphatic malignancies;
- •Liver and kidney function, cardiopulmonary function meet the following requirements:
- •Creatinine ≤ 1.5 ULN;
- •Left ventricular ejection fraction ≥ 45%;
- •blood oxygen saturation>91%;
- •Total bilirubin ≤ 1.5 × ULN； ALT and AST ≤ 2.5 × ULN;
- •Be able to understand the trial and have signed the informed consent.
排除标准
- •Those with graft-versus-host disease (GVHD) or requiring long-term systemic immunosuppressants;
- •Malignant tumors other than CD19-positive hematologic malignancies within 5 years prior to screening, except adequately treated cervical carcinoma in situ, basal cell or squamous epithelial cell skin cancer, local prostate cancer after radical resection, and breast ductal carcinoma in situ after radical resection;
- •Positive for hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and peripheral blood hepatitis B virus (HBV) DNA titer outside the normal reference range; Those who are positive for hepatitis C virus (HCV) antibodies and positive for hepatitis C virus (HCV) RNA in peripheral blood; Human immunodeficiency virus (HIV) antibody positive person; Positive for cytomegalovirus (CMV) DNA testing; those who test positive for syphilis;
- •Serious heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months before screening), congestive heart failure (NYHA classification ≥ III), and serious arrhythmia;
- •Unstable systemic diseases judged by the investigator: including but not limited to severe liver, kidney or metabolic diseases requiring drug treatment;
- •Within 7 days before screening, there is active infection or uncontrollable infection requiring systemic treatment (except for mild genitourinary system infection and upper respiratory tract infection);
- •Pregnant or lactating women, female subjects who planned to conceive within 1 year of cell infusion or male subjects whose partner planned pregnancy within 1 year of their cell infusion;
- •Screening participants (except for inhalation or local use) who were receiving systemic steroid treatment within 7 days before screening or who were judged by the investigator to require long-term systemic steroid therapy during treatment;
- •Participated in other clinical studies within 3 month before screening;
- •There was evidence of central nervous system involvement at participant screening;
- •Conditions that the investigators considered unsuitable for enrollment.
研究组 & 干预措施
UTAA09 cells for infusion
Off-the-shelf γδT cells with a CD19-redirected Chimeric Antigen Receptor. Route of administration: Intravenous injection. Lymphodepleting conditioning regimen: A combination of fludarabine and cyclophosphamide will be administered at Day-7~Day-2.
干预措施: UTAA09 cells for infusion (Biological)
UTAA09 cells for infusion
Off-the-shelf γδT cells with a CD19-redirected Chimeric Antigen Receptor. Route of administration: Intravenous injection. Lymphodepleting conditioning regimen: A combination of fludarabine and cyclophosphamide will be administered at Day-7~Day-2.
干预措施: Fludarabine (Drug)
UTAA09 cells for infusion
Off-the-shelf γδT cells with a CD19-redirected Chimeric Antigen Receptor. Route of administration: Intravenous injection. Lymphodepleting conditioning regimen: A combination of fludarabine and cyclophosphamide will be administered at Day-7~Day-2.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Assessment of the safety after UTAA09 injection treatment
时间窗: About 2 years
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0.
Evaluation of the efficacy after UTAA09 injection treatment
时间窗: About 3 months
3-month total response rate (ORR) which includes CR, CRi, and PR will be assessed.
次要结局
- Assessment of pharmacokinetic (about Cmax)(About 2 years)
- Assessment of pharmacokinetic (about Tmax)(About 2 years)
- Assessment of pharmacokinetic (about AUC0-28d)(About 2 years)
- Assessment of pharmacokinetic (about AUC0-90d)(About 2 years)
- Evaluation of Pharmacodynamic(About 2 years)
- To evaluate the efficacy (Overall Survival)(About 2 years)
- To evaluate the efficacy (Duration Of Response)(About 2 years)
- To evaluate the efficacy (Progression Free Survival)(About 2 years)