A Phase 1 Study Evaluating Safety and Efficacy of C-CAR039 Treatment in Subjects With Relapsed and/or Refractory NHL
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- MTD
研究概览
简要总结
This is a single-arm, open label, dose escalation, phase I study of C-CAR039 in adults with relapsed/refractory B-cell Non-Hodgkin's Lymphoma.
详细描述
This is a single-arm, open label, "3+3" dose escalation, phase I study to evaluate the safety and preliminary efficacy of C-CAR039 in adults with relapsed/refractory B-cell Non-Hodgkin's Lymphoma. 10 patients are planned to be enrolled.
Following consent, enrolled subjects will undergo a leukapheresis procedure to collect autologous mononuclear cells for manufacture of C-CAR039. Following manufacture of the drug product, subjects will receive lymphodepleting therapy with fludarabine and cyclophosphamide prior to C-CAR039 infusion. All subjects who have received C-CAR039 infusion will be followed for up to 24 months.
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
盲法说明
None (Open Label)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The patient volunteered to participate in the study and signed the Informed Consent;
- •Age between 18 and 70 (including 18 and 70), male or female;
- •Expected survival ≥ 12 weeks;
- •ECOG score 0-2
- •CD19 or CD20 positive B-NHL confirmed by cytology or histology according to WHO2016 criteria, including DLBCL, PMBCL, tFL, FL and MCL;
- •Relapsed or refractory disease after ≥ 2 lines (for FL, at least 3 lines) of standard therapy or relapsed after autologous stem cell transplantation (ASCT)
- •For CD20-positive subjects, they should have received at least one regimen containing anti-CD20-targeted therapy (such as rituximab). If they do not complete the regimen due to intolerance, the cause of intolerance should be recorded;
- •No contraindications of apheresis;
- •At least one measurable lesion according to Lugano 2014 criteria;
- •Adequate organ function.
排除标准
- •Malignant tumors other than B-NHL within 5 years prior to screening, except cervical carcinoma in situ, basal cell or squamous cell skin cancer, local prostate cancer after radical surgery, and breast ductal carcinoma in situ after radical surgery;
- •Active HIV, HBV, HCV or treponema pallidum infection ;
- •Any instability of systemic disease, including but not limited to active infection (except local infection), severe cardiac, liver, kidney, or metabolic disease need therapy;
- •Any uncontrolled, active disease that prevents participation in the trial;
- •Female subjects who have been pregnant or breastfeeding, or who plan to conceive during or within 1 year after treatment, or male subjects' partner plans to conceive within 1 year after their cell transfusion;
- •Active or uncontrolled infections requiring systemic treatment within 14 days before enrollment;
- •Patients who have been previously infected with tuberculosis;
- •Administered Corticosteroids and/or other immunosuppressants within 7 days before apheresis. and 5 days before the infusion of C-CAR039;
- •Patients with central nervous system involvement;
- •Any systemic antitumor therapy was performed within 2 weeks before conditional treatment chemotherapy pretreatment;
- •Any situation that the investigator believes would compromise the safety of the subject or interfere with the purpose of the study;
- •Those with medical conditions that prevent them from signing the written informed consent or from complying with the study procedures; or those who are unwilling or unable to comply with the study requirements.
- •Other conditions deemed unsuitable for enrollment by the investigator.
结局指标
主要结局
MTD
时间窗: Up to 24 months after C-CAR039 infusion
maximum tolerated dose or clinical recommended dose
DLT
时间窗: Up to 28 days after C-CAR039 infusion
Dose limiting toxicity
AE/SAE/AESI
时间窗: Up to 24 months after C-CAR039 infusion
adverse events (AE), serious adverse event (SAE), adverse events of sepical interest (AESI) (including cytokine release syndrome (CRS), and nerve toxicity), laboratory tests (type, frequency and severity), vital signs and ECG abnormality rate.
次要结局
- C-CAR039 CAR expansion and persistence(Up to 24 Months after C-CAR039 infusion)
- Overall response rate (ORR)(Up to 24 Months after C-CAR039 infusion)
- Duration of response (DOR)(Up to 24 Months after C-CAR039 infusion)
- Progression-free survival (PFS)(Up to 24 Months after C-CAR039 infusion)
- Overall survival (OS)(Up to 24 Months after C-CAR039 infusion)