A Clinical Study of Sequential CD19/CD22 CAR-T Cell Therapy Following Autologous Stem Cell Transplantation in Relapsed/Refractory Large B-cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Best Complete Response Rate
研究概览
简要总结
The goal of this clinical trial is to learn if sequential CD19/CD22 CAR-T cell therapy following autologous stem cell transplantation (ASCT) works to treat relapsed or refractory large B-cell lymphoma (LBCL) in adults. It will also learn about the safety of this treatment combination. The main questions it aims to answer are:
Does ASCT followed by sequential CD19/CD22 CAR-T therapy improve complete response rates in participants with relapsed/refractory LBCL? What medical problems do participants have when receiving this treatment combination? Researchers will evaluate the safety and efficacy of ASCT followed by sequential CD19/CD22 CAR-T therapy to determine if this treatment approach works to improve outcomes for patients with relapsed/refractory LBCL.
Participants will:
Undergo two separate apheresis procedures for stem cell collection and CAR-T cell manufacturing.
Receive conditioning chemotherapy followed by autologous stem cell infusion on day 0.
Receive sequential CD19 and CD22 CAR-T cell infusions over 3 days within one week post-transplant.Visit the clinic regularly for checkups and tests to monitor their response to treatment and any potential side effects.
Keep a record of their symptoms and any adverse events experienced during the treatment period.
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 with relapsed or refractory large B-cell lymphoma (LBCL) after at least one prior line of therapy.
- •*[Note: LBCL includes: diffuse large B-cell lymphoma, not otherwise specified (DLBCL-NOS); diffuse large B-cell lymphoma transformed from follicular lymphoma (FL-DLBCL); grade 3b follicular lymphoma (FL); primary mediastinal large B-cell lymphoma (PMBCL); high-grade B-cell lymphoma with rearrangements of MYC and BCL-2 and/or BCL-6 (double-hit/triple-hit lymphoma, DHL/THL)].*
- •Age Restriction: Individuals must be 18 to 70 years old.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-
- •Presence of at least one measurable target lesion. *[Note: A target lesion is defined as ≥1 lesion with a longest diameter (LD) >1.5 cm and a longest perpendicular diameter (LPD) ≥1.0 cm, as assessed by computed tomography (CT) or magnetic resonance imaging (MRI).]*
- •Adequate organ function, defined as:
- •Left ventricular ejection fraction (LVEF) ≥50% by echocardiography;
- •Creatinine clearance ≥30 mL/min;
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 × upper limit of normal (ULN).
- •Adequate hematopoietic function, defined as:
- •Platelet count ≥45 ×10⁹/L;
- •Hemoglobin ≥8.0 g/dL;
- •Absolute neutrophil count (ANC) ≥1.0 × 10⁹/L.
- •Life expectancy ≥3 months.
- •For women of childbearing potential, a negative pregnancy test is required. Both male and female patients must agree to use effective contraception during treatment and for 1 year thereafter.
- •Willingness to provide written informed consent.
排除标准
- •Prior allogeneic hematopoietic stem cell transplantation or CAR-T cell therapy.
- •Use of immunosuppressive agents or systemic corticosteroids (equivalent to >10 mg prednisone daily) within 2 weeks prior to leukapheresis, or requirement for continued use after enrollment.
- •Active hepatitis B (HBsAg positive with detectable HBV DNA) or hepatitis C (anti-HCV positive with detectable HCV RNA) infection at screening.
- •Uncontrolled active infection requiring intravenous antimicrobial therapy.
- •History of other malignancies within 2 years prior to enrollment (except adequately treated basal cell carcinoma of skin, squamous cell carcinoma of skin, or carcinoma in situ).
- •Significant comorbidities that may compromise study participation or patient safety, including:
- •Severe cardiovascular disease (NYHA Class III/IV heart failure, myocardial infarction within 6 months, unstable arrhythmias, or angina)
- •Severe pulmonary dysfunction (FEV1 or DLCO ≤50% predicted, or requiring supplemental oxygen)
- •HIV infection (positive serology with detectable viral load).
- •Pregnancy, lactation, or unwillingness to use effective contraception.
- •Any condition that in the investigator's judgment would preclude safe participation.
结局指标
主要结局
Best Complete Response Rate
时间窗: From the date of CAR-T cell infusion until the end of the study, with an average follow-up period of approximately 2 years.
Best Complete Response Rate (CRR), defined as the proportion of patients achieving a best response of complete response according to the Lugano 2014 criteria.
次要结局
- Overall survival(From the date of CAR-T cell infusion until the date of death or last follow-up, assessed up to 5 years.)
- Event-free survival(From the date of CAR-T cell infusion to the date of first event (disease progression, relapse, or death) or last follow-up, assessed up to 5 years.)
- Adverse event(Within 30 days after CAR-T cell infusion)
- Best Overall Response Rate(From the date of CAR-T cell infusion until the end of the study, with an average follow-up period of approximately 2 years.)