Single-center, Open, One-arm Clinical Study of the Safety and Efficacy of Anti-CD56-CAR T Therapy in Relapsed Refractory NK/T Cell Lymphoma /NK Cell Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- progression-free survival (PFS)
研究概览
简要总结
To evaluate the safety and efficacy of anti-CD56-CAR T in the treatment of relapsed refractory NK/T cell lymphoma /NK cell leukemia
详细描述
Extranodal NK/TCL is an aggressive disease with a poor prognosis and a 5-year survival rate of less than 50%. In the absence of effective treatment, median survival for advanced disease is only 6-12 months. A retrospective review of the International Peripheral T-Cell Lymphoma Project recently reported that the median overall survival of NK/TCL was 7.8 months, corresponding to the worst survival of all T-cell lymphoma entities. Therefore, despite good results in the combination of chemoracal-chemotherapy strategies, autologous bone marrow transplantation, and L-asparagase in the treatment of recurrent cases, NK/TCL remains difficult to cure, and the need for alternative therapeutic strategies has prompted researchers to explore new molecular targets.
Nerve cell adhesion molecule 1 (NCAM-1) -CD56 is a member of the immunoglobulin superfamily and is a biomarker of nerve cell adhesion molecule and NK cell. CD56 is highly expressed in NK/T cell lymphomas, skeletal muscle tumors, and malignancies with neurological or neuroendocrine differentiation. CD56-CAR T cells can kill CD56+ neuroblastoma, glioma, and SCLC tumor cells in vitro coculture, and CD56R-CAR+T cells can inhibit tumor growth in vivo when tested against CD56+ human neuroblastoma xenogeneic and SCLC models. CD56-CAR T cells have also been reported as a safe and effective treatment for refractory/relapsing rhabdomyosarcoma. This indicates that CD56 CAR has a wide clinical application prospect and strong potential therapeutic value as a new CAR T target.
CD56 CAR T cells constructed by our laboratory can produce more precise killing effect on tumor cells by converting the immune checkpoint PD-1 signal. The results showed that CD56 CAR T cells could be prepared effectively and kill NK/ T-cell lymphoma cell line SNK-6 in vitro. Compared with traditional second-generation CAR T cells, CD56-CAR T cells prepared in our laboratory showed better killing effect on SNK-6 cells in vitro. At present, no clinical studies on CD56 CAR T therapy for NK/T cell lymphoma have been reported. Therefore, in this study, CD56 CAR T was used to treat relapsed and refractory NK/T cell lymphoma /NK cell leukemia to observe its safety and efficacy.
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
- •Patients or their legal guardians voluntarily participate and sign the informed consent;
- •Male or female patients aged 18-70 years (including 18 and 70 years);
- •The patient was diagnosed as NK/T cell lymphoma /NK cell leukemia by pathology or flow cytometry, and currently has no effective treatment options, such as relapse after chemotherapy or hematopoietic stem cell transplantation; Alternatively, patients voluntarily choose to administer anti-CD56-CAR T cells as salvage therapy.
- •The following two categories are included:(1)NK/T cell lymphoma;(2) NK cell leukemia.
- •(1)There was no remission or residual lesions after treatment, and HSCT (auto/allo-HSCT) was not suitable; (2)Relapse occurred after CR, and HSCT (auto/allo-HSCT) was not suitable; (3)Patients with high risk factors; (4)Relapse or no remission after hematopoietic stem cell transplantation or cellular immunotherapy.
- •Measurable or evaluable lesions;
- •The patient's main tissues and organs function well:
- •Liver function: ALT/AST < 3 times the upper limit of normal (ULN) and total bilirubin ≤34.2μmol/L;
- •Renal function: creatinine < 220 μmol/L;
- •Lung function: indoor oxygen saturation ≥95%;
- •Cardiac function: left ventricular ejection fraction (LVEF) ≥40%.
- •The patients had not received any anti-cancer treatment such as chemotherapy, radiotherapy, immunotherapy (such as immunosuppressive drugs) within the first 4 weeks of enrollment, and their previous treatment-related toxic reactions had recovered to ≤ grade 1 at the time of enrollment (except low toxicity such as hair loss);
- •The patient's peripheral shallow venous blood flow is smooth, which can meet the needs of intravenous infusion;
- •Patients with ECOG score ≤2 and expected survival time ≥3 months.
排除标准
- •Women who are pregnant (urine/blood pregnancy test positive) or breastfeeding;
- •Men or women who have planned to become pregnant within the last 1 year;
- •The patients were not guaranteed to take effective contraceptive measures (condoms or contraceptives, etc.) within 1 year after enrollment;
- •Patients had uncontrollable infectious diseases within 4 weeks prior to enrollment;
- •Active hepatitis B/C virus;
- •HIV-infected patients;
- •Suffering from a serious autoimmune disease or immunodeficiency disease;
- •The patient is allergic to antibodies, cytokines and other macromolecular biological drugs;
- •The patient had participated in other clinical trials within 6 weeks prior to enrollment;
- •Systemic use of hormones within 4 weeks prior to enrollment (except for inhaled hormones);
- •Suffers from mental illness;
- •The patient has substance abuse/addiction;
- •According to the researchers' judgment, the patient had other conditions that were not suitable for inclusion.
结局指标
主要结局
progression-free survival (PFS)
时间窗: From 1 month to 1 year.
The time between treatment and observation of disease progression or death from any cause.
Safety evaluation index
时间窗: From 1 month to 1 year.
1. Detection of CRS-related factors: such as IFN, IL-6, TNF, IL-10, IL-4, CRP, etc;2. Testing of various laboratory items: blood routine, coagulation function, blood film observation, liver function, renal work, electrolytes, blood glucose, cardiac enzymes, blood cells, T cell subsets, immunoglobulins, etc;3.Adverse events and serious adverse events were observed.
Overall response rate (ORR)
时间窗: From 1 month to 1 year.
CR+PR.1.Leukemia:Complete Response (CR):Bone marrow blast cells \<5%; primitive cells without Auer bodies; without extramedullary leukemia;Absolute blood neutrophil count was\> 1.0\*10\^9 / L (1000 / μ L);Platelet count\> 100\*10\^9 / L (100 000 / μ L);Not dependent on RBC infusion.Partial Response (PR):Only for Phase I and II clinical trials;Bone marrow cells were reduced to 5 - 25% and at least 50% compared with before treatment;Hematological parameters met the same criteria for CR. 2.Lymphoma:CR:All the evidence of the lesions disappeared.PR:The lymph nodes shrank with no new lesions.
event-free survival (EFS)
时间窗: From 1 month to 1 year.
The time between the start of treatment and the occurrence of any event, including disease recurrence, death, and so on.
overall survival (OS)
时间窗: From 1 month to 1 year.
The time from the start of treatment to death from any cause.
次要结局
- CAR T cell index of correlation(From 1 month to 1 year.)