A Study Evaluating the Safety, Tolerability, and Pharmacokinetics of LUCAR-20S in Patients With Relapsed/Refractory Diffuse Large B-Cell, Follicular, Mantle Cell or Small Lymphocytic Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 7
- 试验地点
- 3
- 主要终点
- Dose limiting toxicity (DLT)
研究概览
简要总结
An open label, single arm Phase I study to evaluate the safety, tolerability, and pharmacokinetics of LUCAR-20S CAR-T cells in relapsed or refractory CD20+ diffuse large B-cell, follicular, mantle cell and small lymphocytic lymphoma.
详细描述
This study is an open, dose escalation/dose regimen finding study to assess the safety and pharmacokinetics of donor-derived CD20-directed CAR-T cells administered with lymphodepletion, and to obtain the preliminary efficacy results in subjects who have been diagnosed with relapsed or refractory CD20 positive diffuse large B-cell lymphoma, follicular lymphoma, mantle cell lymphoma or small lymphocytic lymphoma. The allo-CAR-T cells will be infused in single-dose.
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
- •Signed informed consent form (ICF)
- •Age 18 Years to 75 Years
- •Pathological diagnosis of refractory/relapsed CD20+ non-Hodgkin's lymphoma (one of the following):
- •Diffuse large B-cell lymphoma (DLBCL)
- •Follicular lymphoma (FL)
- •Mantle cell lymphoma (MCL)
- •Small lymphocytic lymphoma (SLL)
- •Measurable disease as defined by 2014 Lugano criteria at Screening
- •Refractory/relapsed disease after standard-of- care treatment as following (Undergone at least 2 complete cycle of therapy for each line, unless PD been documented as the best response to the regimen) and not eligible or appropriate for HSCT (Auto/allo). Subject must have documented evidence of progressive disease on or within 12 months of their last regimen.
- •DLBCL: Refractory/relapsed after at least 1 prior line of therapy, must have been treated with anti-CD20 monoclonal antibody
- •FL: Refractory/relapsed after at least 2 prior lines of therapy, must have been treated with anti-CD20 monoclonal antibody
- •MCL: Refractory/relapsed after at least 2 prior lines of therapy
- •SLL: Refractory/relapsed after at least 2 prior lines of therapy
- •Laboratory criteria at Screening
- •① Blood routine: NE≥1.0×109/L；HGB≥8g/dL；PLT≥50×109/L
- •② Blood biochemical parameters:
- •Total bilirubin ≤ 1.5 times of the normal upper limit (ULN)
- •Aspartate and alanine aminotransferases (AST, ALT) ≤ 3 times ULN (in the presence of liver metastasis, ULN 5 times)
- •Estimated glomerular filtration rate (eGFR) > 60mL/min
- •Life expectancy > 12 weeks
- •Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 or 1
排除标准
- •Any malignancy besides the NHL categories under study, exceptions include
- •Any other malignancy curatively treated and disease-free for at least 2 years prior to enrollment
- •History of non-melanoma skin cancer with sufficient treatment and currently no evidence of recurrence
- •Prior treatment with an allogeneic stem cell transplant
- •Prior treatment with genetic therapy
- •Prior treatment with chimeric antigen receptor T (cells) CAR-T therapy directed at CD20 target
- •Those who are positive for any index of hepatitis B surface antigen (HBsAg), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C antibody (HCV-Ab), hepatitis C virus ribonucleic acid (HCV RNA), and human immunodeficiency virus antibody (HIV-Ab)
- •Prior antitumor therapy with insufficient washout period
- •Targeted therapy, epigenetic therapy, experimental drug therapy or experimental invasive treatment with medical apparatus and instruments 14 days or five half-lives, whichever is shorter before lymphodepletion
- •Use of monoclonal antibodies 21 days prior to lymphodepletion
- •Chemotherapy within 14 days prior to lymphodepletion
- •Radiotherapy within 14 days prior to lymphodepletion
- •Participated in other clinical trials within 30 days prior to lymphodepletion
- •With central nervous system involvement
- •Women in pregnancy or lactation
- •Being fertile and unable to use effective conception during treatment and 100 days after CAR-T infusion
- •Active autoimmune disease or history of autoimmune disease within 3 years
- •With obvious hemorrhagic tendency such as gastrointestinal hemorrhage, coagulation disorders and hypersplenism
- •The following cardiac conditions
- •New York Heart Association (NYHA) stage III or IV congestive heart failure
- •Left ventricular ejection fraction (LVEF) less than (<)45%
- •Uncontrolled cardiac arrhythmia post-medication
- •With a history of myocardial infraction or unstable angina pectoris within the past 6 months
- •Constrictive pericarditis
- •Cardiomyopathy
- •Pulse oximetry of <96% on room air
- •Active or uncontrolled infection requiring parenteral antibiotics, or any evidence of severe active viral/bacterial infection or uncontrolled systemic fungal infection
- •Uncontrolled diabetes mellitus, defined as fast serum glucose > 1.5 times ULN
- •Concurrent use of corticosteroids or other immunosuppressant medications for chronic disease
- •Concurrent use of hematopoietic growth factor
- •Stroke or seizure within 6 months of signing ICF
- •Have received any live, attenuated vaccine within 4 weeks prior to lymphodepletion
- •Have underwent major surgical operation within 2 weeks prior to lymphodepletion, or anticipate to undergo a major surgical operation during the study process or within 2 weeks posterior to study treatment(with the exception of anticipated local anesthesia surgery)
- •Known life threatening allergies, hypersensitivity, or intolerance to LUCAR-20S CAR-T cells or its excipients, including dimethyl sulfoxide (DMSO)
- •Presence of any condition that, in the opinion of the investigator, would prohibit the patient from undergoing treatment under this protocol
研究组 & 干预措施
Anti-CD20 Allogeneic CAR-T Cell Therapy
An open label, single arm Phase I study to evaluate the safety, tolerability, and pharmacokinetics of LUCAR-20S CAR-T cells in relapsed or refractory CD20+ diffuse large B-cell, follicular, mantle cell and small lymphocytic lymphoma.
干预措施: LUCAR-20S CAR-T cells (Drug)
结局指标
主要结局
Dose limiting toxicity (DLT)
时间窗: 30 days post infusion
DLT assessed by NCI-CTCAE 5.0
Concentration of Pharmacokinetics in blood
时间窗: through study completion, 2 years after infusion of the last subject
PK CAR positive T cells in peripheral blood, PK CAR transgene levels in peripheral blood
Adverse events
时间窗: 90 days post infusion
Incidence and severity of adverse events as assessed by NCI-CTCAE 5.0
Concentration of Pharmacokinetics in bone marrow
时间窗: through study completion, 2 years after infusion of the last subject
PK CAR positive T cells in bone marrow, PK CAR transgene levels in bone marrow
次要结局
- Overall response rate (ORR) after administration(3 months post infusion)
- Recommended Phase II dose (RP2D)(30 days post infusion)
- Time to Response (TTR) after administration(3 months post infusion)
- Duration of remission (DOR) after administration(through study completion, 2 years after infusion of the last subject)
- Progress Free Survival (PFS) after administration(through study completion, 2 years after infusion of the last subject)
- Overall Survival (OS) after administration(through study completion, 2 years after infusion of the last subject)
研究者
WEI XU
Chief Physician of hematology department
The First Affiliated Hospital with Nanjing Medical University