Prospective, Single-center, Single-arm, Open-label Study of Obinutuzumab, Zanubrutinib and Lenalidomide Sequential CD19/CD22 CAR-T in Patients With Relapsed or Refractory B-Cell Non-Hodgkin Lymphoma
试验速览
- 阶段
- 不适用
- 状态
- Enrolling By Invitation
- 发起方
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Overall response rate (ORR) after GZL therapy
研究概览
简要总结
This study intends to use Obinutuzumab, Zanubrutinib, and Lenalidomide sequential CD19/CD22 CAR-T in the treatment of Relapsed or Refractory B-cell Non-Hodgkin Lymphoma patients. The main purpose of this study is to explore a new treatment mode for R/R B-NHL patients and observe the efficacy and safety of this treatment regimen.
详细描述
The study will start with 2-4 cycles of combination chem-free therapy with obinutuzumab, zanubrutinib and lenalidomide, followed by sequential CAR-T therapy. CAR-T therapy with AZA + FC (Azacitidine +Fludarabine +Cyclophosphamide) conditioning regimen. Targets of CAR-T cells are CD19/CD22. In this clinical trial, ORR, CRR, OS, PFS, AE and other indicators were used to observe the safety and efficacy of this sequential therapy.
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
- •Histologically confirmed CD22 + and/or CD19 + aggressive B-cell non-Hodgkin lymphoma (NHL), including the following types as defined by World Health Organization (WHO) 2016:
- •Diffuse large B-cell lymphoma (DLBCL); High grade B-cell lymphoma (HGBL); Primary mediastinal large B-cell lymphoma(PMBCL); T cell/histiocyte-rich large B-cell lymphoma (THRBCL); High grade follicular cell lymphoma Grade 3b (3bFL); Mantle cell lymphoma (MCL) except indolent; Other aggressive B-cell lymphomas.
- •Disease refractory to first-line therapy or early relapse within 12 months of last treatment.
- •Relapse or progressive disease (PD) ≥ 3 months after targeted CD19 therapy including CD19 CAR T cells or anti-CD19/anti-CD
- •Successful leukapheresis assessment and T-cell preculture.
- •Life expectancy > 3 months.
- •Appropriate organ function:
- •Creatinine < 1.6 mg/dL (140 µmol/L) or creatinine clearance ≥ 60ml/min; Alanine aminotransferase (ALT)/aspartate aminotransferase (AST) < 3 × upper limit of normal; Bilirubin < 2.0 mg/dL unless subject has Gilbert 's syndrome (< 3.0 mg/dL); Pulmonary reserve ≤ Grade 1 dyspnea and SPO2 > 91%; Cardiac ejection fraction ≥ 50% in the absence of oxygen, no evidence of pericardial effusion as determined by echocardiogram (ECHO), and no clinically significant electrocardiogram (ECG) findings.
- •Adequate bone marrow reserve was defined as:
- •Absolute neutrophil count (ANC) > 1000/mm3; Absolute lymphocyte count (ALC) ≥ 300/mm3; Platelet count ≥ 50,000/mm
- •Hemoglobin > 7.0 mg/dL.
- •Measurable or evaluable lesions according to "IWG response criteria for malignant lymphoma" (Cheson 2014).
- •Patients have the ability to understand and are willing to provide written informed consent.
排除标准
- •severe liver and kidney dysfunction (alanine aminotransferase, bilirubin, creatinine > 3 times the upper limit of normal);
- •the presence of structural heart disease, and lead to clinical symptoms or abnormal heart function (NYHA ≥ 2);
- •uncontrolled active infection;
- •the presence of other tumors requiring treatment or intervention;
- •the current or expected need for systemic corticosteroid therapy;
- •pregnant or lactating women.
- •Other psychological conditions that prevent patients from participating in the study or signing informed consent;
- •According to the investigator 's judgment, the subject is unlikely to complete all protocol-required study visits or procedures, including follow-up visits, or fail to meet the requirements for participation in the study.
研究组 & 干预措施
GZL sequential CD19/CD22 CAR-T
Phase I (combined immunotherapy period):
2-4 cycle of combination chem-free therapy with Obinutuzumab, Zanubrutinib and Lenalidomide . Each cycle is 21 days.
Phase II (CAR-T therapy):
CAR-T therapy with AZA + FC (Azacitidine, Fludarabine and Cyclophosphamide) conditioning regimen. Targets of CAR-T cells are CD19/CD22.
干预措施: Obinutuzumab (Drug)
GZL sequential CD19/CD22 CAR-T
Phase I (combined immunotherapy period):
2-4 cycle of combination chem-free therapy with Obinutuzumab, Zanubrutinib and Lenalidomide . Each cycle is 21 days.
Phase II (CAR-T therapy):
CAR-T therapy with AZA + FC (Azacitidine, Fludarabine and Cyclophosphamide) conditioning regimen. Targets of CAR-T cells are CD19/CD22.
干预措施: Zanubrutinib (Drug)
GZL sequential CD19/CD22 CAR-T
Phase I (combined immunotherapy period):
2-4 cycle of combination chem-free therapy with Obinutuzumab, Zanubrutinib and Lenalidomide . Each cycle is 21 days.
Phase II (CAR-T therapy):
CAR-T therapy with AZA + FC (Azacitidine, Fludarabine and Cyclophosphamide) conditioning regimen. Targets of CAR-T cells are CD19/CD22.
干预措施: Lenalidomide (Drug)
GZL sequential CD19/CD22 CAR-T
Phase I (combined immunotherapy period):
2-4 cycle of combination chem-free therapy with Obinutuzumab, Zanubrutinib and Lenalidomide . Each cycle is 21 days.
Phase II (CAR-T therapy):
CAR-T therapy with AZA + FC (Azacitidine, Fludarabine and Cyclophosphamide) conditioning regimen. Targets of CAR-T cells are CD19/CD22.
干预措施: CD19/CD22 CAR-T (Drug)
GZL sequential CD19/CD22 CAR-T
Phase I (combined immunotherapy period):
2-4 cycle of combination chem-free therapy with Obinutuzumab, Zanubrutinib and Lenalidomide . Each cycle is 21 days.
Phase II (CAR-T therapy):
CAR-T therapy with AZA + FC (Azacitidine, Fludarabine and Cyclophosphamide) conditioning regimen. Targets of CAR-T cells are CD19/CD22.
干预措施: Azacitidine For Injection (Drug)
GZL sequential CD19/CD22 CAR-T
Phase I (combined immunotherapy period):
2-4 cycle of combination chem-free therapy with Obinutuzumab, Zanubrutinib and Lenalidomide . Each cycle is 21 days.
Phase II (CAR-T therapy):
CAR-T therapy with AZA + FC (Azacitidine, Fludarabine and Cyclophosphamide) conditioning regimen. Targets of CAR-T cells are CD19/CD22.
干预措施: Fludarabine (Drug)
GZL sequential CD19/CD22 CAR-T
Phase I (combined immunotherapy period):
2-4 cycle of combination chem-free therapy with Obinutuzumab, Zanubrutinib and Lenalidomide . Each cycle is 21 days.
Phase II (CAR-T therapy):
CAR-T therapy with AZA + FC (Azacitidine, Fludarabine and Cyclophosphamide) conditioning regimen. Targets of CAR-T cells are CD19/CD22.
干预措施: Cyclophosphamide (Drug)
结局指标
主要结局
Overall response rate (ORR) after GZL therapy
时间窗: At the end of GZL therapy (2-4 cycles, each cycle is 21days)
the rate of patients who achieved CR or PR after GZL therapy
Progression-free survival (PFS) after CAR-T
时间窗: up to 24 months after the end of last patient's treatment
PFS will be assessed from the GZL combination therapy given to date of progression, relapse, death or end of follow-up.
Complete response rate (CRR) after CAR-T
时间窗: Within 3 months after CAR-T therapy
the best rate of patients who achieved CR after CAR-T therapy
次要结局
- Duration of Response(DOR) after CAR-T(up to 24 months after the end of last patient's treatment)
- Overall response rate (ORR) after CAR-T(Within 3 months after CAR-T therapy)
- Incidence of treatment-emergent adverse events, treatment-related adverse events and serious adverse events(Initiation of GZL therapy until 30 days after CAR-T therapy)
- Overall survival (OS) after CAR-T(up to 24 months after the end of last patient's treatment)