CD19/ CD22 Bispecific CAR-T Cell Therapy for Relapsed/ Refractory Large B-cell Lymphoma: A Prospective, Single-Arm, Single-Center, Phase 2 Trial
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- best overall response rate (ORR) as of 3 months post-CAR-T cells infusion
研究概览
简要总结
CAR-T cell therapy targeting CD19 has been shown to be effective in heavily-pretreated B-cell ALL or NHL, but relapses post-CAR-T are common, and CD19 antigen loss is one of the reasons. Thus, the investigators supposed that CD19/CD22 bispecific CAR-T cell therapy would be more effective and less relapses would occur in B- NHL. In this prospective phase 2 clinical trial, the investigators aim to explore the efficacy and safety of CD19/CD22 bispecific CAR-T cell therapy in relapsed/refractory Large B cell lymphoma.
详细描述
Large B cell lymphoma (LBCL) is the most common aggressive subtype of non-Hodgkin lymphoma (NHL) in adults. While approximately 60% of patients can be cured with first-line therapy, a subset of patients experiences relapse or refractory disease (R/R). The prognosis for R/R LBCL patients is poor, with limited efficacy from traditional treatments such as autologous stem cell transplantation (ASCT) and novel targeted agents. Chimeric antigen receptor-T (CAR-T) cell therapy involves genetically engineering T cells to express chimeric antigen receptors (CARs) that target tumor-specific antigens, enabling precise elimination of tumor cells. CD19 is the most commonly targeted antigen in B-cell malignancies, however, antigen escape following CD19 CAR-T therapy can lead to disease relapse in some patients. Studies indicate that CD22 is widely expressed in B-cell malignancies and exhibits incomplete overlap with CD19 expression, suggesting that dual-target CAR-T therapy may more comprehensively eradicate tumor cells. Therefore, dual-target CAR-T therapy, particularly strategies targeting both CD19 and CD22, has emerged as a promising approach to overcome antigen escape and enhance therapeutic outcomes. In this prospective study, the investigators aimed to evaluate the efficacy and safety of CD19/CD22 bispecific CAR-T cell (CAR2219) therapy in patients with R/R LBCL.
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
- 14 Years 至 85 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •14 years to 85 years, expected survival > 3 months;
- •CD19 positive with or without CD22 positive Large B-cell lymphoma;
- •relapsed or refractory disease;
- •ECOG-PS score=0-2;
- •Having at least one measurable lesion;
- •Cardiac function: 1-2 levels;
- •Liver: TBIL≤3ULN，AST ≤2.5ULN，ALT ≤2.5ULN;
- •kidney: Cr≤1.25ULN;
- •bone marrow: WBC ≥ 3.0×10e9/L, Hb ≥80 g/L, PLT ≥ 50×10e9/L;
- •No serious allergic constitution;
- •No other serious diseases that conflicts with the clinical program;
- •No other cancer history;
- •No serious mental disorder;
- •Informed consent is signed by a subject or his lineal relation.
排除标准
- •Pregnant or lactating women (female participants of reproductive potential must have a negative serum or urine pregnancy test);
- •Uncontrolled active infection, HIV infection, syphilis serology reaction positive;
- •Active hepatitis B or hepatitis C infection;
- •With severe cardiac, liver, renal insufficiency, diabetes and other diseases;
- •Participate in other clinical research in the past 4 weeks;
- •Researchers think of that does not fit to participate in the study, or other cases that affect the clinical trial results.
研究组 & 干预措施
CD19/CD22 CAR-T group
Patients would receive autologous CAR-T cell therapy targeting both CD19 and CD22. The dosage for CD19/CD22 bispecific CAR-T cells was 2×10e6/kg.
干预措施: CD19/CD22 bispecific CAR-T cells (Drug)
结局指标
主要结局
best overall response rate (ORR) as of 3 months post-CAR-T cells infusion
时间窗: From the day of CAR-T cells infusion to 3 months post-CAR-T cells infusion
Overall response rate means sum of complete response rate and partial response rate
次要结局
- Best Complete Response rate (CR) as of 3 months post-CAR-T cells infusion(From the day of CAR-T cells infusion to 3 months post-CAR-T cells infusion)
- Progression free survival (PFS)(From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion)
- overall survival (OS)(From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion)
- Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability](From the day of CAR-T cells infusion to 12 months post-CAR-T cells infusion)
研究者
LIANG WANG
Director of Department of Hematology
Beijing Tongren Hospital