NCT05531708撤回1 期
Safety and Efficacy Study of Novel Mesothelin CAR-T Cell Therapy in Patients With Mesothelin-positive Advanced Refractory Solid Tumors
Shanghai Pudong Hospital1 个研究点 分布在 1 个国家开始时间: 2021年4月2日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 试验地点
- 1
- 主要终点
- AESIs
研究概览
简要总结
This is a single-arm, open-label, exploratory clinical study to evaluate the safety and efficacy of novel Mesothelin CAR-T in patients with Mesothelin-positive advanced refractory solid tumors.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Solid tumors positive for the Mesothelin antigen by Immunohistochemistry/Immunocytochemistry (IHC/ICC); histological diagnosis of malignancy refractory to, or relapsing after standard therapy.
- •At least one measurable lesion according to RECIST v1.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Life expectancy ≥ 3 months.
- •Neutrophils ≥ 1.0×10^9/L; Lymphocytes ≥ 0.5×10^9/L; Hemoglobin ≥ 80 g/L; Platelets ≥ 75×10^9/L.
- •Adequate hepatic, renal, cardiac and coagulation function defined as:
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.5 × upper limit of normal (ULN); patients with liver metastasis must be ≤ 5 × ULN;
- •Total bilirubin (TBIL) ≤ 1.5 × ULN; TBIL of patients with Gilbert's Syndrome must less than 3.0 mg/dL;
- •Serum creatinine (Cr) ≤ 1.5 × ULN, and creatinine clearance rate (Ccr) ≥ 60 mL/min;
- •Left ventricular ejection fraction (LVEF) > 45%;
- •Prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN.
- •Negative screen for infectious disease markers including HIV-Ab, HCV-Ab, HBeAg, HBsAg, and syphilis. Note - Participants with history of prior HBV infection are eligible if the HBV viral load is undetectable. Participants with a history of HCV infection who were treated for hepatitis C and cured are eligible if hepatitis C viral load is undetectable.
- •The toxicities from any prior therapy must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo) according to NCI CTCAE v5.
- •The washout period of previous treatment:
- •Cytotoxic chemicals, monoclonal antibodies or immunotherapy should be washed out for at least 4 weeks before leukapheresis; anti-CTLA-4 antibodies should be washed out for at least 6 weeks;
- •Systemic corticosteroids or other immunosuppressive therapies should be washed out for at least 2 weeks before leukapheresis;
- •Biologicals or other approved molecular targeted inhibitors should be eluted for at least 1 week or 5 half-lives (whichever is longer) prior to leukapheresis.
- •Participants must be able to understand the protocol and be willing to enroll the study, sign the informed consent, and be able to comply with the study and follow-up procedures.
排除标准
- •Patients with central nervous system involvement.
- •Patients with clinically significant systemic disease (such as: severe active infection or significant cardiac, pulmonary, hepatic, nervous system, or other organ dysfunction) that evaluated by the investigator would impair the patient's ability to tolerate the treatments used in this study or significantly increase the risk of complications.
- •Any known or suspected autoimmune disease; or active, chronic or recurrent immune-mediated disease (within one year prior to enrollment) requiring steroid or other immunosuppressive therapy.
- •History of severe systemic hypersensitivity reaction to the drugs/ingredients used in this study.
- •Have received any allogeneic tissue/organ transplantation (including bone marrow transplantation, stem cell transplantation, liver transplantation, kidney transplantation), except for the transplantation that does not require immunosuppressive therapy (such as: corneal transplantation, hair transplantation.)
- •Have received any genetic engineering modified T cell therapy (including CAR-T, TCR-T).
- •History of major surgery and unrecovered severe trauma within 4 weeks prior to signing informed consent.
- •History of another malignancy tumor, except for non-melanoma skin cancer and carcinoma in situ of bladder, stomach, colon, cervix/dysplasia, melanoma, or breast.
- •History of neuropsychiatric diseases diagnosed by the ICD-11 criteria or evaluated by investigator.
- •For any other reasons, the patients are believed not suitable for participation in this study by investigators.
研究组 & 干预措施
Anti-mesothelin CAR-T cells
Experimental
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, anti-mesothelin CAR-T cells.
干预措施: Anti-mesothelin CAR-T cells (Biological)
Anti-mesothelin CAR-T cells
Experimental
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, anti-mesothelin CAR-T cells.
干预措施: Fludarabine (Drug)
Anti-mesothelin CAR-T cells
Experimental
A conditioning chemotherapy regimen of fludarabine and cyclophosphamide will be administered followed by investigational treatment, anti-mesothelin CAR-T cells.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
AESIs
时间窗: 4 weeks after the CAR-T cells infusion
Incidence and severity of AEs of special interest.
TEAEs
时间窗: 4 weeks after the CAR-T cells infusion
Incidence and severity of treatment emergent adverse events.
TRAEs
时间窗: 4 weeks after the CAR-T cells infusion
Incidence and severity of treatment related adverse events.
次要结局
- Duration of Overall Response（DOR）(24 months)
- Objective Response Rate (ORR) (PR+CR)(12 weeks)
研究者
研究点 (1)
Loading locations...
相似试验
尚未招募
1 期
MSLN-targeted CAR-T Cells in Solid Tumors.Mesothelin-positive Advanced Malignant Solid TumorsNCT05783089Cancer Institute and Hospital, Chinese Academy of Medical Sciences87
Unknown
早期 1 期
The Fourth Generation CART-cell Therapy for Refractory-Relapsed Ovarian CancerOvarian CancerNCT03814447Shanghai 6th People's Hospital10
招募中
1 期
A Clinical Study of CHT102 in MSLN-Positive Advanced Pancreatic CancerAdvanced Pancreatic CancersNCT06760364Tianjin Medical University Cancer Institute and Hospital21
已完成
1 期
Autologous Redirected RNA Meso CAR T Cells for Pancreatic CancerSubjects With Metastatic Pancreatic Ductal Adenocarcinoma (PDA)NCT01897415University of Pennsylvania16
已完成
1 期
Phase 1 Study of Mesothelin-ADCAdvanced CancerNCT02884726Bristol-Myers Squibb8