A Prospective, Open-label and Single-arm Study of Anti-PD1 Armored CD19 CAR-T Cells in Adult Subjects With Relapsed or Refractory Diffuse Large B-cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Incidence of dose-limiting toxicity (DLT)
研究概览
简要总结
The purpose of this study is to investigate the safety and tolerability of anti-PD1 armored CD19 CAR-T Cells in adult subjects with relapsed or refractory diffuse large B-cell lymphoma.
详细描述
This is a prospective, open-label, single-arm clinical study to evaluate the safety, tolerability of anti-PD1 armored CD19 CAR-T Cells in adult subjects with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL).The study plans to explore across three dose levels (1.00 × 10^6, 3.00 × 10^6, 9.00 × 10^6 CAR+ T cells/kg), and 6.00×10^8 CAR+T cells as maximum dose, aiming to evaluate the safety, tolerability of anti-PD1 armored CD19 CAR-T Cells in r/r DLBCL, explore Maximum Tolerated Dose (MTD) and determine the recommended dose for Phase II. Besides, efficacy, pharmacokinetics and persistence profile of CAR-T cells are also study objectives.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •1. Subjects voluntarily participate in clinical research and sign informed consent.
- •2. Adult subjects (age ≥18 ) with relapsed or refractory diffuse large B-cell lymphoma: a) failure to achieve CR after 6 cycles, or PR after 3 cycles, of first-line therapy, or achieve CR after first-line therapy but relapse within 12 months; b) achieve CR after systemic treatment, but are refractory or relapsed, and no plan to transplant, or prepare for transplantation but cannot meet transplantation criteria after second-line therapy; c) not achieve CR after at least two courses of second-line treatment (including autologous stem cell transplantation).
- •3. Expected survival ≥ 3 months.
- •4. At least one measurable lesion as per revised IWG response criteria for malignant lymphom (2014 Lugano criteria).
- •5. CD19 positive expression are detected on tumor cells of subjects by flow cytometry or immunohistochemistry.
- •6. ECOG score ≤
- •7. Subjects with adequate organ functions prior to enrollment, meet the following laboratory values:
- •Renal function: serum creatinine ≤ 1.5 × ULN or estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m².
- •Hepatic function: Serum alanine aminotransferase (ALT) ≤ 5 × age-specific ULN and total bilirubin ≤ 2.0 mg/dL, except in subjects with Gilbert-Meulengracht syndrome. If total bilirubin ≤ 3.0 × ULN and direct bilirubin ≤ 1.5 × ULN, subjects with Gilbert-Meulengracht syndrome are included.
- •Pulmonary reserve: ≤ Grade 1 dyspnea and oxygen saturation >95% on room air.
- •8. Stable hemodynamics and left ventricular ejection fraction (LVEF) ≥ 45 % assessed by echocardiography or multi-gated radionuclide angiography (MUGA).
- •9. Adequate bone-marrow reserve without blood transfusion as defined by:
- •Absolute neutrophil count (ANC) ≥ 1 x 10^9/L.
- •Absolute lymphocyte count (ALC) ≥ 0.1 x 10^9/L.
- •Platelets ≥ 50 x 10^9/L.
- •Hemoglobin >80g/L.
- •10. In the investigator's judgment, subjects' general condition and all biochemical values are either normal or sufficiently compensated to receive lymphodepletion and CAR-T cell therapy.
排除标准
- •1. Women who are pregnant or breastfeeding, or planned pregnancy within 6 months.
- •2. Infectious disease(HIV, Active Tuberculosis ect.).
- •3. Active infection: hepatitis B, hepatitis C.
- •4. Abnormal vital signs or refuse to receive examination.
- •5. Subjects with psychiatric or psychological disorders are unable to complete treatment or efficacy assessment.
- •6.History of severe hypersensitivity or known hypersensitivity to IL-
- •7. Systemic or local severe infection requiring antimicrobial therapy.
- •8. Significant dysfunction of vital organs (heart, lung, brain, kidney, etc.), or in the investigator's judgment, subjects are unable to be enrolled with any other condition.
研究组 & 干预措施
Anti-PD1 armored CD19 CAR-T cells treatment arm
Subjects will be administrated with Anti-PD1 armored CD19 CAR-T cells after lymphocyte depletion by fludarabine and cyclophosphamide.
干预措施: Anti-PD1 armored CD19 CAR-T cells (Biological)
结局指标
主要结局
Incidence of dose-limiting toxicity (DLT)
时间窗: 1 month after injection
Dose-limiting toxicity for each subject
AE/SAE
时间窗: 1 month, 3 months, 6 months, 12 months after injection
Incidence and severity of adverse events (AE), and serious adverse event (SAE)
次要结局
- Objective response rate (ORR)(1 month, 3 months, 6 months, 9 months, 12 months after injection)
- Overall survival (OS)(1 month, 3 months, 6 months, 9 months, 12 months after injection)
- Duration of response (DOR)(1 month, 3 months, 6 months, 9 months, 12 months after injection)
- Progression-free survival (PFS)(1 month, 3 months, 6 months, 9 months, 12 months after injection)