A Single-Center, Prospective Study Evaluating the Efficacy and Safety of Glofitamab Combined With CAR-T Therapy in Patients With High-Risk Relapsed/Refractory Large B-Cell Lymphoma
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 24
- 主要终点
- Complete Response Rate (CRR)
概览
简要总结
This study is a single-center, open-label, prospective study aimed at evaluating the efficacy and safety of Glofitamab combined with CAR-T therapy in patients with high-risk relapsed/refractory large B-cell lymphoma.
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
- •Signed Informed Consent Form
- •Histologically confirmed large B==cell lymphoma with CD19 and CD20 expression, including diffuse large B==cell lymphoma (DLBCL) not otherwise specified (NOS); primary mediastinal large B==cell lymphoma (PMBCL); high==grade B==cell lymphoma (HGBL); and DLBCL transformed from follicular lymphoma
- •Patients who have relapsed after at least one prior line of therapy or are refractory, including those who have received anthracycline==containing chemotherapy regimens and anti==CD20 monoclonal antibody therapy
- •Patients must be willing to receive CAR==T and Glofitamab therapy and be deemed suitable for CAR==T and Glofitamab treatment by the investigator
- •Presence of at least one high==risk prognostic factor: (1) extranodal involvement; (2) maximum tumor diameter \> 4 cm; (3) TP53 mutation
- •No CNS involvement
- •ECOG Performance Status of 0, 1, or 2
- •Life expectancy ≥12 weeks
- •Adequate hematologic function (unless due to underlying disease, such as extensive bone marrow involvement, or secondary to lymphoma==related splenomegaly as determined by the investigator, but transfusion of blood products is allowed) and adequate liver, renal, pulmonary, and cardiac function, defined as follows:
- •Neutrophil count ≥ 1.0 × 10\^9/L, platelet count ≥ 50 × 10\^9/L, lymphocyte count ≥ 0.1 × 10\^9/L
排除标准
- •History of allergic reactions to compounds with similar chemical or biological composition to axi==cel, relma==cel, glofitamab, obinutuzumab, or other drugs used in the study.
- •Active or uncontrolled infections requiring systemic therapy (including fungal, bacterial, viral, etc.)
- •History of allogeneic hematopoietic stem cell transplantation
- •History of organ transplantation
- •Viral infections deemed uncontrollable by antiviral medications, as determined by the investigator, including:
- •Active hepatitis B virus (HBV) infection with HBV DNA ≥ 500 IU/mL (2500 copies/mL)
- •Positive hepatitis C virus (HCV) RNA test
- •Positive human immunodeficiency virus antibody (HIV==Ab) test
- •Positive Treponema pallidum antibody (TP==Ab) test
- •Cytomegalovirus (CMV) DNA levels above the upper limit of normal
研究组 & 干预措施
Glofit_CART
After undergoing leukapheresis, patients will receive treatment in three phases: the bridging phase, the CAR-T treatment phase, and the consolidation phase.
Bridging Phase:
All patients will receive two cycles of Glofitamab treatment. On Day 1 of Cycle 1, patients will receive 1000 mg of Obinutuzumab as pretreatment.
After the completion of Cycle 2, patients will undergo an assessment.
CAR-T Treatment Phase:
Participants will receive lymphodepletion therapy with the FLU/CY regimen from Day -5 to Day -3.
On Day 0, patients will receive the CAR-T cell infusion.
Consolidation Phase:
Based on the efficacy assessment on Day 28, the subsequent treatment plan will be determined: Patients achieving complete response (CR) will not receive additional Glofitamab treatment.
Patients with partial response (PR), stable disease (SD), or progressive disease (PD) will continue to receive Glofitamab treatment for four additional cycles.
干预措施: Glofitamab (Drug)
Glofit_CART
After undergoing leukapheresis, patients will receive treatment in three phases: the bridging phase, the CAR-T treatment phase, and the consolidation phase.
Bridging Phase:
All patients will receive two cycles of Glofitamab treatment. On Day 1 of Cycle 1, patients will receive 1000 mg of Obinutuzumab as pretreatment.
After the completion of Cycle 2, patients will undergo an assessment.
CAR-T Treatment Phase:
Participants will receive lymphodepletion therapy with the FLU/CY regimen from Day -5 to Day -3.
On Day 0, patients will receive the CAR-T cell infusion.
Consolidation Phase:
Based on the efficacy assessment on Day 28, the subsequent treatment plan will be determined: Patients achieving complete response (CR) will not receive additional Glofitamab treatment.
Patients with partial response (PR), stable disease (SD), or progressive disease (PD) will continue to receive Glofitamab treatment for four additional cycles.
干预措施: Obinutuzumab (Drug)
Glofit_CART
After undergoing leukapheresis, patients will receive treatment in three phases: the bridging phase, the CAR-T treatment phase, and the consolidation phase.
Bridging Phase:
All patients will receive two cycles of Glofitamab treatment. On Day 1 of Cycle 1, patients will receive 1000 mg of Obinutuzumab as pretreatment.
After the completion of Cycle 2, patients will undergo an assessment.
CAR-T Treatment Phase:
Participants will receive lymphodepletion therapy with the FLU/CY regimen from Day -5 to Day -3.
On Day 0, patients will receive the CAR-T cell infusion.
Consolidation Phase:
Based on the efficacy assessment on Day 28, the subsequent treatment plan will be determined: Patients achieving complete response (CR) will not receive additional Glofitamab treatment.
Patients with partial response (PR), stable disease (SD), or progressive disease (PD) will continue to receive Glofitamab treatment for four additional cycles.
干预措施: Axicabtagene Ciloleucel (Drug)
Glofit_CART
After undergoing leukapheresis, patients will receive treatment in three phases: the bridging phase, the CAR-T treatment phase, and the consolidation phase.
Bridging Phase:
All patients will receive two cycles of Glofitamab treatment. On Day 1 of Cycle 1, patients will receive 1000 mg of Obinutuzumab as pretreatment.
After the completion of Cycle 2, patients will undergo an assessment.
CAR-T Treatment Phase:
Participants will receive lymphodepletion therapy with the FLU/CY regimen from Day -5 to Day -3.
On Day 0, patients will receive the CAR-T cell infusion.
Consolidation Phase:
Based on the efficacy assessment on Day 28, the subsequent treatment plan will be determined: Patients achieving complete response (CR) will not receive additional Glofitamab treatment.
Patients with partial response (PR), stable disease (SD), or progressive disease (PD) will continue to receive Glofitamab treatment for four additional cycles.
干预措施: Relmacabtagene autoleucel (relma-cel) (Drug)
结局指标
主要结局
Complete Response Rate (CRR)
时间窗: Baseline up to the end of treatment (EOT) (approximately 4 months)
Assessed by Investigator per Lugano Response Criteria for Malignant Lymphoma
次要结局
- Overall Response Rate (ORR)(Baseline up to the EOT (approximately 4 months))
- Duration of Response (DoR)(From the date of the first occurrence of a documented CR or partial response (PR) to the date of progression, relapse, or death from any cause, whichever occurs first (up to approximately 42 months))
- PFS(From the start of treatment until the first occurrence of disease progression or relapse, or death from any cause, whichever occurs earlier (approximately 42 months))
- Overall Survival (OS)(From the start of treatment until the date of death from any cause (approximately 42 months))
- Number of Participants with TEAEs(Up to the end of the study (approximately 42 months))