CLS-015-TAMSC-LBCL-PR An Exploratory, Investigator Initiated Study to Assess the Safety of Combination of CLS-015 (DFF) With Anti-CD-19 CAR-T Cells in Patients With Stable/ Progressive Large B Cell Lymphoma at Lymphodepletion.
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- To evaluate the safety and tolerability of CLS-015 in combination with anti CD19 CAR T therapy in subjects with stable/progressive Large B-Cell lymphoma at lymphodepletion when CLS-015 is given in adjuvant setting.
研究概览
简要总结
This is a Phase 1, single-center, open-label study to evaluate the safety of CLS-015 in combination with anti-CD19 CAR-T therapy in patients with large B-cell lymphoma. The goal is to improve clinical response by reversing the negative effects of NETs on immune function and CAR-T cells.
详细描述
Disease progression in large B-cell lymphoma is a major obstacle to successful CAR-T therapy, with approximately 40% of patients experiencing disease progression within 3 months of CAR-T infusion and 60% of patients experiencing disease progression within the first year.
While patients with large B-cell lymphoma in partial response or complete response during lymphodepletion have a progression-free survival (PFS) of 60-80% at 1 year, patients with stable disease (SD) or progressive disease (PD) in the lymphodepletion phase have a poor PFS of 20-30%.
Patients with SD/PD in the lymphoid depletion phase, particularly those with low CAR-T concentrations on day +7, are at very high risk of early disease progression after CAR-T infusion, and there is an urgent and unmet medical need to improve their outcomes.
Preclinical studies have shown that CLS-015 enhances the performance of CAR T-cell therapy against CD19-expressing malignancies through various mechanisms, including enhancing CAR T-cell activity, preventing T-cell exhaustion, reducing cytokine release syndrome (CRS), and enhancing CAR-T cell penetration into areas with lymphoma cells by enzymatically degrading NETs in tumor tissue and the bloodstream.
All patients enrolled in the study with large B-cell lymphoma in SD/PD during lymphodepletion will receive CLS-015 on days 0, 3, 6, 10, and 15 after CAR-T cell infusion, as an intravenous infusion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 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
- •Participant must be at least 18 years of age inclusive, at the time of signing the informed consent.
- •Large B-Cell lymphoma treated with CAR-T targeting CD19 (tisagenlecleucel, axicabtagene ciloleucel, or lisocabtagene maraleucel)
- •Stable Disease or Progressive Disease confirmed by PET-CT on the day of lymphodepletion
- •Capable of giving signed informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
排除标准
- •Hypersensitivity to CLS-015
- •Evidence of any clinically significant condition, disorder, condition, or disease that, in the opinion of the Investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
- •Active infection requiring antibiotics
- •Females only: Pregnant or breastfeeding
研究组 & 干预措施
CLS-015 infusions after CAR-T infusion
CLS-015 infusions will be done on Days 0,3,6,10 and 15 after CAR-T infusion
干预措施: rhDNase I (Drug)
结局指标
主要结局
To evaluate the safety and tolerability of CLS-015 in combination with anti CD19 CAR T therapy in subjects with stable/progressive Large B-Cell lymphoma at lymphodepletion when CLS-015 is given in adjuvant setting.
时间窗: Through study completion, an average of 2 years.
Safety and tolerability of CLS-015 based on adverse events evaluation and recording will be evaluated from screening to the end of study.
次要结局
未报告次要终点