A Clinical Study Evaluating the Safety and Efficacy of Universal CD19-Targeted CAR-T (UWD-CD19) Therapy for Refractory and Relapsed B-Cell Tumors
试验速览
- 阶段
- 早期 1 期
- 状态
- 暂停
- 发起方
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Maximum Tolerated Dose (MTD)
研究概览
简要总结
This study is a single-arm, single-center, investigator-initiated clinical trial. The primary objective is to evaluate the safety and preliminary efficacy of administering universal CD19 CAR-T cells to subjects with refractory and relapsed B-cell tumors. Eligible participants will undergo FC lymphodepleting chemotherapy preconditioning after signing an informed consent form, followed by a one-time injection of universal UWD-19 to assess its safety and efficacy. Subjects will be hospitalized for a period, and after discharge, they will undergo periodic efficacy assessments and long-term survival follow-up for at least five years.
详细描述
This study is a single-arm clinical trial evaluating the universal CD19-targeted CAR-T cell therapy (UWD-CD19) in treating relapsed and refractory B-cell tumors. Initiated by investigators, the study aims to assess the safety and preliminary efficacy of this cell therapy, providing new therapeutic options for patients with B-cell tumors-a class of hematologic malignancies that often recur and resist standard treatments, posing substantial treatment challenges.
CD19 is a specific marker predominantly expressed on the surface of B-cells, making it a prime target for CAR-T cell therapies. CAR-T therapy involves extracting T cells from a healthy donor and genetically engineering them to recognize and attack CD19-expressing tumor cells. UWD-CD19, a "universal" CAR-T cell product, seeks to enhance therapy adaptability, allowing it to effectively target B-cell tumors across different patient groups.
Study Objectives The primary objective of this study is to observe the therapeutic response in patients with relapsed or refractory B-cell tumors through a single infusion of UWD-CD19, specifically focusing on safety, tolerability, and preliminary efficacy. The research team will also conduct long-term follow-up on patients to assess the durability of treatment effects and survival rates, providing data support for the potential wider application of this novel therapy.
Inclusion Criteria: Patients aged between 3 and 70, with no gender restrictions, must meet diagnostic criteria for B-cell lymphoma with CD19-positive tumor cells. Patients should have an evaluable or measurable lesion as defined by the 2014 Lugano criteria.
Preconditioning: Eligible patients will receive lymphodepleting chemotherapy with Fludarabine and Cyclophosphamide before cell infusion to suppress the immune system and optimize CAR-T cell performance.
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
- 3 Years 至 70 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients (or their guardians) understand the study and voluntarily sign the informed consent form, with an expected ability to complete follow-up evaluations and treatments as per study protocol.
- •Age range: 3-70 years, no gender restrictions. Diagnosis of B-cell lymphoma, meeting the 2018 NCCN B-Cell Lymphoma guidelines (Version 5), with CD19 positivity confirmed by flow cytometry or immunohistochemistry.
- •At least one evaluable or measurable lesion per Lugano 2014 criteria. Evaluable lesions are indicated by FDG uptake above liver levels on FDG/PET or by lymphoma-like characteristics on PET/CT. Measurable lesions require a nodal diameter >15 mm or extranodal lesion >10 mm (with post-radiation evidence of progression if previously irradiated). Cases without measurable lesions but with diffuse liver FDG uptake are excluded.
- •Refractory and relapsed B-cell lymphoma, meeting at least one of the following: a. Received ≥2 cycles of standardized second-line or higher treatment, and meets Lugano 2014 criteria for best clinical response:
- •Progressive Disease (PD) on the most recent treatment.
- •Stable Disease (SD) lasting <6 months before progressing. b. Recurrence or progression ≤12 months post-autologous stem cell transplant. c. Based on investigator judgment, the potential benefit may outweigh risk in cases such as:
- •Recent SD with measurable disease progression but not meeting PD criteria. Partial remission (PR) or better lasting <6 months post-treatment, then progression.
- •Intolerance to most recent chemotherapy. Relapsed/refractory CD19-positive acute B lymphoblastic leukemia.
- •Laboratory values indicating adequate organ and marrow function, with no severe cardiac, pulmonary, hepatic, renal, or immune dysfunction:
- •Serum albumin ≥25 g/L Creatinine clearance ≥30 mL/min/1.73 m² ALT and AST ≤3.0× ULN Total bilirubin ≤2.0× ULN (exceptions for congenital hyperbilirubinemia like Gilbert syndrome with direct bilirubin ≤1.5× ULN) PT and APTT <2× ULN Oxygen saturation ≥95% Blood transfusions allowed to maintain hemoglobin ≥8.0 g/dL. ECOG performance status 0-
- •Expected survival time >90 days. Negative β-hCG test for women of childbearing potential at screening and prior to chemotherapy.
- •Women of childbearing potential must use a highly effective contraceptive method (annual failure rate <1%) from the time of consent until 1 year after UWD-CD19 infusion, including:
- •Non-user-dependent: implantable progestogen, IUD, hormone-releasing system, or partner vasectomy.
- •User-dependent: combination hormonal contraception, progestogen-only pill, or injection.
排除标准
- •History of aggressive malignancies other than B-cell lymphoma, except:
- •Cancer in remission >2 years post-curative therapy. Non-melanoma skin cancer successfully treated and inactive.
- •Prior anti-cancer therapy including:
- •Targeted, epigenetic, or experimental drug therapy within 14 days or 5 half-lives.
- •Cytotoxic therapy within 14 days. Immunomodulators within 7 days. Monoclonal antibodies within 21 days. Radiotherapy within 14 days. Active CNS involvement. Conditions like Waldenström's macroglobulinemia, POEMS syndrome, or primary AL amyloidosis.
- •Active hepatitis B (HBsAg or HBcAb positive with viral load >1000 copies/ml), hepatitis C (HCV RNA positive), HIV, CMV, or syphilis positivity.
- •Severe allergy history, or known allergy to trial components, adjuvants, or animal-derived proteins.
- •Severe cardiac conditions such as arrhythmias, unstable angina, recent MI, heart failure (NYHA III/IV), uncontrolled hypertension.
- •Unstable systemic disease, including significant liver, kidney, or metabolic disease requiring medication.
- •Acute/chronic GVHD or requiring immunosuppressants within 6 months. Active autoimmune or inflammatory neurologic diseases. Urgent tumor-related conditions requiring emergency treatment. Uncontrolled bacterial, fungal, or viral infections. Major surgery within 4 weeks or planned major surgery during the study. Live virus vaccination within 4 weeks prior to screening. Severe psychiatric disorders. History of substance abuse. Pregnant or lactating women, or individuals planning conception within 2 years of cell infusion.
- •Any contraindications per investigator's judgment due to clinical standards or patient's condition.
研究组 & 干预措施
Off-the-shelf REVO-UWD-19
Eligible participants will undergo FC lymphodepleting chemotherapy preconditioning, followed by a one-time injection of universal UWD-19 cells
干预措施: Single dose injection of certain dose of UWD-19 (Biological)
结局指标
主要结局
Maximum Tolerated Dose (MTD)
时间窗: [Time Frame: Within the first month post-infusion.]
The highest dose of UWD-19 CAR-T cells that can be administered without causing unacceptable side effects, measured during the dose escalation phase.
Dose-Limiting Toxicities (DLT)
时间窗: [Time Frame: Within the first month post-infusion.]
The incidence of treatment-related toxicities that prevent further dose escalation.
Treatment-Emergent Adverse Events (TEAE)
时间窗: [Time Frame: From the administration of UWD-19 CAR-T cells through six months post-infusion]
The frequency and severity of adverse events that arise following the administration of UWD-19-CAR-T cells.
次要结局
- Objective Response Rate (ORR)([Time Frame: Measured at 3 and 6 months after treatment.])
- Progression-Free Survival (PFS)([Time Frame: From the start of treatment up to 5 years.])
- Overall Survival (OS)([Time Frame: From the start of treatment up to maximum follow-up period of five years.])
- Duration of Response (DOR)([Time Frame: From the administration of UWD-19 CAR-T cells to a maximum follow-up period of five years.])