Clinical Study on the Safety and Efficacy of Chimeric Antigen Receptor Gene Modified T Cells Targeting CD30 in the Treatment of CD30 Positive Relapsed/Refractory Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- To evaluate safety and dose limiting toxicities (DLT) of autologous CD30 CAR-T and establish the recommended Phase dose
研究概览
简要总结
The is a prospective, open-label, dose-climbing multicenter clinical study assessing the efficacy and safety of CD30 CAR-T in the treatment of r/r CD30+ lymphoma. Plan to recruit 15 subjects with r/r CD30+ lymphoma。
详细描述
The goal of this clinical trial is to explore the efficacy and safety of CD30 CAR-T on CD30 positive relapsed/refractory lymphoma. The main questions it aims to answer are:
To evaluate the safety and maximum tolerated dose of autologous CD30 CAR-T therapy in CD30-positive relapsed/refractory lymphoma; To evaluate the efficacy of autologous CD30 CAR-T therapy for CD30-positive relapsed/refractory lymphoma; To evaluate the metabolism of CD30 CAR-T cells in vivo; Preliminary evaluation of the correlation between CAR T cell dose and clinical efficacy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age≥18 years and ≤65years，female and male；
- •CD30+ recurrent/refractory malignant hematological malignancies, experienced recurrence (disease progression after treatment remission) or refractory (previous systemic treatment did not achieve CR) after ≥ 2-line systemic treatment;
- •CD30 expression >10% by immunohistochemistry；
- •At least 1 measurable lesion can be measured according to theLugano 2014 evaluation criteria;
- •The estimated survival time ≥3 months;
- •ECOG performance status 0-2，KPS>60%;
- •Sufficient organ function：ALT，AST≤2.5×ULN，patients with liver invasion can be relaxed to ≤ 5 x ULN；serum total bilirubin<34 μmol/L；creatinine clearance rate>30 mL/min；EF≥40%；No pericardial effusion and obvious arrhythmia；SpO2≥92%；
- •ALC ≥0.5×109/L，PLT>30×109/L，Hb>80 g/L and subjects had apheresis venous access and no contraindications for blood cell separation;
- •MRI showed no central involvement of lymphoma;
- •Patients with fertility must be willing to be able to use reliable contraceptive measures ;
- •The subject or legal guardian can understand and voluntarily sign the written informed consent.
排除标准
- •Lymphoma-associated hemophagic cell syndrome;
- •Pregnant or lactating women, and women who have a pregnancy plan within six months;
- •Hepatitis B（HBsAg、HBsAb、HBeAg、HBeAb、HBcAb），Hepatitis C（Anti-HCV），Anti-HIV Ⅰ/Ⅱ and anti-TP positive（Hepatitis B DNA test is negative except）;
- •Suffered from other malignant tumors, except for for skin basal cell carcinoma, skin squamous cell carcinoma and cervical carcinoma in situ undergoing the radical treatment;
- •Received Anti-CD30 Ab therapy within 4 weeks before enrollment;
- •Unresolved > Grade 1 non-hematologic toxicity associated with any prior treatments;
- •Active uncontrolled bleeding or a known bleeding diathesis;
- •Autologous hematopoietic stem cell transplantation was performed within 6 weeks;
- •Uncontrollable active bacterial or fungal infection；
- •Known allergy to the study drug and its components;
- •Suffer from active autoimmune diseases that require systemic treatment ;
- •Persons with mental or mental illness who cannot cooperate with treatment and efficacy evaluation;
- •Participated in other clinical studies within 1 months prior to this study;
- •History of allogeneic hematopoietic stem cell transplantation;
- •patients with any condition which the investigator or treating physician feels would interfere with the trial or the safety of the subject.
研究组 & 干预措施
Group3
Subjects received a single high-dose CD30 CAR-T therapy
干预措施: chimeric antigen receptor gene modified T cells (Drug)
Group1
Subjects received a single low-dose CD30 CAR-T therapy
干预措施: chimeric antigen receptor gene modified T cells (Drug)
Group2
Subjects received a single medium-dose CD30 CAR-T therapy
干预措施: chimeric antigen receptor gene modified T cells (Drug)
结局指标
主要结局
To evaluate safety and dose limiting toxicities (DLT) of autologous CD30 CAR-T and establish the recommended Phase dose
时间窗: 28 days
Incidence of DLTs and occurrence of study related adverse events
次要结局
- Overall Survival(3 years)
- Overall response rate(3,6,12months)
- Progression-free survival(3 years)