A Single Dose-escalation Study to Evaluate the Safety and Efficacy of Allogeneic CAR-T Targeting CD19 (ThisCART19A) in Adult Patients With B Cell Malignancies After Failure of Autologous Chimeric Antigen Receptor T- Cell(CAR-T) Therapy
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Minimum Residual Disease (MRD) Negative Remission Rate within 3 months during dose expansion stage
研究概览
简要总结
This is a a phase 1, open label study to assess the safety and efficacy of ThisCART19 (Allogeneic CAR-T targeting CD19) in adult patients with B cell malignancies after failure of autologous chimeric antigen receptor T- cell(CAR-T) therapy in china.
详细描述
This is a phase 1, single-center, nonrandomized, open-label, dose-escalation and dose expansion study to evaluate the safety and efficacy of ThisCART19A in adult patients with B cell malignancies after failure of autologous chimeric antigen receptor T- cell(CAR-T) therapy and identify a treatment regimen most likely to result in clinical efficacy while maintaining a favorable safety profile.
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
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient with relapsed or refractory acute lymphocytic leukemia, or lymphoma；
- •No gender limitation, Age 14 years to 75 years (both upper and lower limits included)；
- •Failing to autologous CAR-T therapy；
- •Should be confirmed Cluster of differentiation(CD)19 positive；
- •The expected survival time is ≥12 weeks;
- •ECOG score 0-1;
- •Measurable or detectble disease at time of enrollment.
- •Adequate bone marrow, renal, hepatic, pulmonary and cardiac function；
排除标准
- •Allergic to preconditioning measures；
- •Patients with other malignancies other than B-cell malignancies within 5 years prior to screening. Patients with cured skin squamous carcinoma, basal carcinoma, non-primary invasive bladder cancer, localized low-risk prostate cancer, in situ cervical/breast cancer can be recruited；
- •Uncontrollable bacterial, fungal and viral infection during screening；
- •Patients had pulmonary embolism (PE) and/or deep vein thrombosis (DVT) within 3 months prior to enrollment;
- •Had intolerant severe cardiovascular and cerebrovascular diseases and hereditary diseases prior to enrollment；
- •The presence of central nervous system involvement；
- •Active hepatitis B virus (HBV) or hepatitis C virus (HCV) or Human immunodeficiency virus (HIV) or Syphilis infection. HBV-DNA < 2000 IU/mL can be enrolled, but should admitted to use anti-virus drugs such as entecavir, tenofovir, etc, and supervisory the relative indication during the treatment；
- •Had big lesion(single lesion diameter ≥10 cm)；
- •Receive allogeneic hematopoietic stem cell transplantation less than 100 days；
- •Vaccinated with influenza vaccine within 2 weeks prior to cleansing (SARS-COV19 can be included, inactivated, live/non-live adjuvant vaccinations allowed to be included)；
- •Patients who are receiving GvHD treatment; Patients without GvHD and who had stopped immunosuppressive drugs for at least 1 month were eligible for inclusion；
- •Women who are in pregnant or lactating, and female subjects or partners who plan to be pregnant within 1 year after cell infusion. Male subjects who plan pregnancy within 1 year after infusion.
研究组 & 干预措施
ThisCART19A cells infusion
In this study, allogeneic anti-CD19 CAR T cell (ThisCART19A) infusion is used to treat patients with refractory or relapsed CD19 positive B cell acute lymphoblastic leukemia.
干预措施: ThisCART19A (Drug)
ThisCART19A cells infusion
In this study, allogeneic anti-CD19 CAR T cell (ThisCART19A) infusion is used to treat patients with refractory or relapsed CD19 positive B cell acute lymphoblastic leukemia.
干预措施: Fludarabine Pill (Drug)
ThisCART19A cells infusion
In this study, allogeneic anti-CD19 CAR T cell (ThisCART19A) infusion is used to treat patients with refractory or relapsed CD19 positive B cell acute lymphoblastic leukemia.
干预措施: Cyclophosphamide (Drug)
ThisCART19A cells infusion
In this study, allogeneic anti-CD19 CAR T cell (ThisCART19A) infusion is used to treat patients with refractory or relapsed CD19 positive B cell acute lymphoblastic leukemia.
干预措施: VP-16 Protocol (Drug)
结局指标
主要结局
Minimum Residual Disease (MRD) Negative Remission Rate within 3 months during dose expansion stage
时间窗: 3 months
MRD was assessed utilizing multicolor flow cytometry to detect residual cancerous cells with a sensitivity of 10\^-4. MRD negative remission was defined as MRD \< 10\^-4 threshold. Percentage of participants with MRD negative remission was reported.
Objective Response Rate within 3 months during dose expansion stage
时间窗: 3 months
For Acute Lymphoblastic Leukemia (ALL), Objective response rate(ORR) is the percentage of patients who achieve Complete Response (CR) or Complete Response With Incomplete Hematologic Recovery (CRi); for lymphoma, ORR is the incidence of either a complete response (CR) or a partial response (PR).
Dose limited toxicity(DLT) observation in patient with B Cell Malignancy in each dose level during dose escalation stage
时间窗: 28 days
DLT is defined as the incidence of severe adverse events related to ThisCART19A more than 33% in each dose level.
次要结局
- Overall Survival (OS)(24 months)
- Duration of response(DOR) during dose escalation stage and expansion stage(24 months)
- Event-free Survival (EFS)(24 months)
- Relapse-free Survival (RFS)(24 months)