A Phase II, Multicenter Study of GlOfitamab in Patients With Mantle Cell Lymphoma and inaDequate Response or Relapse Following CAR T-cell Therapy (GOLD)
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 41
- 试验地点
- 14
- 主要终点
- Complete Response Rate (CRR)
概览
简要总结
This is a Phase 2, multicentre, single arm study that evaluates the efficacy and safety of glofitamab in MCL patients with inadequate response or relapse following CAR T-cell therapy.
详细描述
This is a Phase 2, multicentre, single arm study that evaluates the efficacy and safety of glofitamab in MCL patients with inadequate response or relapse following CAR T-cell therapy. Patients experiencing failure after CAR-T cell treatment will be screened for inclusion and exclusion criteria for treatment and, if eligible, will enter the study.
Safety events will be analyzed and compared with the previously described safety profile of glofitamab alone and other bispecific-containing regimens to exclude the risk of potential toxicity for all study participants.
The study will include a period of screening phase, a period of treatment phase and a follow up phase.
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
- •Able to provide written informed consent forms approved by the National Ethics Committee (NEC) prior to the initiation of any screening or study-specific procedures and able to understand and to comply with the requirements of the study and the schedule of assessments.
- •Histologically confirmed MCL after CAR T-cells failure (CD20+ by flow cytometry or immunohistochemistry). Note: Availability of archival material is mandatory for the study to perform central pathology review. Central pathology confirmation is not required to start treatment.
- •Patients who received CAR T-cells therapy for R/R MCL at least 30 days prior to signing the informed consent form and who meet one of the following situations:
- •Stable disease (SD) or progressive disease (PD) up to D+90; after CAR T-cells infusion (from D+30 to D+90);
- •Partial response (PR) at D+90 after CAR-T cells infusion;
- •Relapsed disease at any time after CAR-T cells infusion.
- •No persistent CAR-T neurotoxicity symptoms or previous experience during CAR T-cells therapy of severe neurotoxicity grade \> 3
- •Adverse events from prior anti-cancer therapy must have resolved to Grade ≤ 1 (hematological toxicities excepted).
- •Adequate hematological counts are defined as follows:
- •Absolute neutrophil count (ANC) \> 1.0 x 109/L unless due to bone marrow involvement by lymphoma;
排除标准
- •Prior exposure to an anti-CD20xCD3 bispecific antibody (bsAbs).
- •Participants not able to give consent.
- •History of treatment-emergent immune-related adverse events associated with prior immunotherapeutic agents, as follows:
- •Grade ≥ 3 adverse events except for Grade 3 endocrinopathy managed with replacement therapy;
- •Grade 1-2 adverse events that did not resolve to baseline after treatment discontinuation.
- •Patients with history of macrophage activation syndrome (MAS) / hemophagocytic lymphohistiocytosis (HLH).
- •Allogeneic hematopoietic stem cell transplantation.
- •History of progressive multifocal leukoencephalopathy (PML).
- •History of autoimmune disease, including, but not limited to myocarditis, pneumonitis, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
- •CNS involvement with lymphoma.
研究组 & 干预措施
Single arm
Patients enrolled and with confirmed eligibility will be treated according to the following schedule:
- Obinutuzumab (2000 mg) will be administered 7 days before (Day 1, Cycle1) the first glofitamab dose;
- Glofitamab treatment for 12 cycles: intravenous glofitamab will be administered with step-up dosing on D8 (2.5mg), D15 (10mg) of Cycle (C) 1 and at 30mg on D1 of C2-12 (21-day cycles).
干预措施: Glofitamab (Drug)
结局指标
主要结局
Complete Response Rate (CRR)
时间窗: 27 months
Complete Response Rate (CRR) at the end of treatment (C12) (assessed by the independent review committee according to Lugano 2014 criteria) and at any time during study treatment.
次要结局
- Overall Response Rate (ORR)(27 months)
- Complete Response Rate (CRR)(27 months)
- Progression Free Survival (PFS)(51 months)
- Overall Survival (OS)(51 months)
- Duration of Response (DOR)(51 months)
- Time to Next Treatment (TTNT)(51 months)
- Event Free Survival (EFS)(51 months)
- AEs(51 months)