A Phase I, Multicenter Study to Evaluate the Safety, Tolerability, and Efficacy of LCAR-T2C CAR-T Cells in Relapsed or Refractory CD4+ T Lymphocyte Tumor Patients
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Recommended Phase II dose (RP2D)
研究概览
简要总结
This is a multicenter phase I clinical study evaluating the safety, tolerability, and efficacy of LCAR-T2C cell agents targeting CD4 in patients with relapsed/refractory CD4-positive T lymphocytic tumors. Thirty-three subjects will be enrolled. Subjects will be pretreated with chemotherapy prior to infusion of CAR T cells: about 5 days before cells transfusion, the patients who planned to reinfuse CAR T cells were treated with fluorodarabine 30 mg/m2( body surface area) and cyclophosphamide 300 mg/m2( body surface area) for 3 days. hen this study will be using a 3+3 dose escalation approach from dose 1 (DL-1): 5×105 to dose 2 (dl-2): 1.5×106 , to dose 3 (dl-3): 5×106 to dose 4 (dl-4): 10.0×106. Below the lowest dose was reinfused at the PI's discretion.
详细描述
This is an open, dose escalation/dose extension study of LCAR-T2C CAR-T cells administered to patients with T lymphocyte tumor. The aim of the study is to evaluate the safety, tolerability, and efficacy of LCAR-T2C CAR-T cells. The auto-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 CD4+ T lymphocyte tumor (one of the following):
- •a. T-cell Non-Hodgkin lymphoma(T-NHL)：The best response is progressive disease(PD) or stable disease(SD) after at least 1 prior line of therapy（at least 2 complete cycle of therapy） b. T-cell Acute lymphoblastic leukemia(T-ALL)：The best response is not complete response(CR) after induction therapy
- •Measurable disease is necessary at Screening
- •Life expectancy ≥ 3 months
- •Eastern Cooperative Oncology Group (ECOG) Performance Status grade of 0 -
- •The screening phase clinical laboratory values meet the following criteria. Laboratory test(s) may be repeated once, to determine if the subject qualifies for study participation :
- •Blood routine:
- •HGB≥6g/dL；PLT≥20×10^9/L; ANC≥1.0×10^9/L; LY≥0.3×10^9/L
- •Blood biochemical parameters:
- •Aspartate and alanine aminotransferases (AST, ALT) ≤ 2.5 times ULN (in the presence of liver metastasis, AST and ALT≤5 times ULN)
- •Serum creatinine (Scr) ≤ 1.5 times ULN, estimated glomerular filtration rate (eGFR) > 60mL/min (only when Scr>1.5 times ULN)
- •Total bilirubin ≤ 1.5 times of the normal upper limit (ULN)
- •International Normalized Ratio (INR) ≤ 1.5 times ULN, PT≤ 1.5 times ULN, APTT≤ 1.5 times ULN
排除标准
- •Prior treatment with CAR-T therapy directed at any target.
- •Any therapy that is targeted to CD
- •Prior treatment with an allogeneic stem cell transplant
- •Any malignancy besides the T lymphocyte tumor 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
- •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)
- •The following cardiac conditions:
- •New York Heart Association (NYHA) stage III or IV congestive heart failure
- •Myocardial infarction or coronary artery bypass graft (CABG) 6 months prior to enrollment
- •History of clinically significant ventricular arrhythmia or unexplained syncope, not believed to be vasovagal in nature or due to dehydration
- •History of severe non-ischemic cardiomyopathy
- •Impaired cardiac function (LVEF <45%) as assessed by echocardiogram or multiple-gated acquisition (MUGA) scan (performed ≤8 weeks of apheresis)
- •Prior antitumor therapy as follows, prior to apheresis:
- •Targeted therapy, epigenetic therapy, or treatment with an investigational drug or used an invasive investigational medical device within 14 days or at least 5 half-lives, whichever is less.
- •Monoclonal antibody treatment for multiple myeloma within 21 days.
- •Cytotoxic therapy within 14 days.
- •Radiotherapy within 14 days.
- •Participated in other clinical trials within 30 days.
- •Toxicity from previous anticancer therapy must resolve to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy.
- •With central nervous system involvement.
- •Serious underlying medical condition, such as:
- •a. Evidence of serious active viral, bacterial, or uncontrolled systemic fungal infection b. Active or unstable autoimmune diseases or autoimmune diseases that have been suffered within 3 years and have the possibility of recurrence c. Overt clinical evidence of dementia or altered mental status
- •Pregnant or breast-feeding, or planning to become pregnant while enrolled in this study or within 100 days after receiving study treatment.
- •Plans to father a child while enrolled in this study or within 100 days after receiving study treatment.
- •With obvious hemorrhagic tendency such as gastrointestinal hemorrhage, coagulation disorders and hypersplenism
- •Oxygen is needed to maintain sufficient blood oxygen saturation(≥95%)
- •Suffer from chronic diseases that require treatment with systemic corticosteroids or other immunosuppressive agents ,Received a cumulative dose of corticosteroids equivalent to ≥20 mg/day of prednisone within 7 days prior to apheresis
- •CNS diseases with clinical significance in the past or at the time of screening
- •Vaccinated with live, attenuated vaccine within 4 weeks prior to apheresis
- •Major surgery within 2 weeks prior to apheresis, or has surgery planned during the study or within 2 weeks after study treatment administration. (Note: subjects with planned surgical procedures to be conducted under local anesthesia may participate.)
- •Known life threatening allergies, hypersensitivity, or intolerance to LCAR-T2C CAR-T cells or its excipients, including DMSO (refer to Investigator's Brochure)
- •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
LCAR-T2C CAR-T cells in relapsed or refractory CD4+ T lymphocyte tumor
An open label, multi center, single arm Phase I study to evaluate the safety, tolerability, and efficacy of LCAR-T2C CAR-T cells in relapsed or refractory CD4+ T lymphocyte tumor.
干预措施: Efficacy of LCAR-T2C CAR-T cells (Drug)
结局指标
主要结局
Recommended Phase II dose (RP2D)
时间窗: 30 days post infusion
RP2D established through ATD+BOIN design and the DLTs occurring following CAR T-cell infusion
Dose limiting toxicity (DLT)
时间窗: 30 days post infusion
DLT assessed by NCI-CTCAE 5.0
Anti-drug antibody
时间窗: 2 years post infusion
Anti-drug antibody (ADA) will be conducted on blood sample for immune response analyses.
Adverse events
时间窗: 90 days post infusion
Incidence and severity of adverse events as assessed by NCI-CTCAE 5.0
Concentration of PK CAR positive T cells in peripheral blood and bone marrow
时间窗: 2 years post infusion
PK CAR positive T cells in peripheral blood, PK CAR transgene levels in peripheral blood, PK CAR positive T cells in bone marrow and PK CAR transgene levels in bone marrow.
次要结局
未报告次要终点