A Phase 1, Open-label, Dose Escalating Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of the Combination of CLBR001 and SWI019 in Patients With Relapsed/Refractory B-cell Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 18
- 试验地点
- 15
- 主要终点
- Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events
研究概览
简要总结
CLBR001 + SWI019 is an combination investigational immunotherapy being evaluated as a potential treatment for patients diagnosed with B cell malignancies who are refractory or unresponsive to salvage therapy or who cannot be considered for or have progressed after autologous hematopoietic cell transplantation. This first-in-human study will assess the safety and tolerability of CLBR001 + SWI019 and is designed to determine the maximum tolerated dose (MTD) or optimal SWI019 dose (OSD). Patients will be administered a single infusion of CLBR001 cells followed by cycles of SWI019. The study will also assess the pharmacokinetics and pharmacodynamics of CLBR001 + SWI019.
详细描述
CLBR001 + SWI019 is a two-component therapy comprising an autologous chimeric antigen receptor T (CAR-T) cell product (CLBR001, the switchable CAR-T cell (sCAR-T)) and an anti-CD19 (cluster of differentiation antigen 19) antibody (SWI019, the switch, a biologic). In combination, SWI019 acts as an adapter molecule that controls the activity of the CLBR001 CAR-T cell product.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 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
- •Patients with relapsed / refractory previously treated B cell malignancies (according to the World Health Organization classification; 2017)
- •Patients must have received adequate prior therapy including at least two lines of prior therapies including anthracycline or bendamustine-containing chemotherapy, anti-CD20 (cluster of differentiation antigen 20) therapies and/or Brutton's tyrosine kinase (BTK) inhibitors
- •Patients treated with prior CD19 targeted molecules (e.g., Blincyto) must have confirmed CD19+ disease
- •Patients must be ineligible for allogeneic stem cell transplant (SCT)
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or 1
- •Estimated life expectancy of ≥ 12 weeks from the first day of SWI019 dose administered
- •Willing to undergo pre- and post-treatment core needle biopsy
- •Adequate hematological, renal, pulmonary, cardiac, and liver function
- •Resolved adverse events of any prior therapy to either baseline or CTCAE Grade ≤1
- •Women of childbearing potential, a negative pregnancy test and must agree to practice effective birth control
- •Men sexually active with female partners of child bearing potential must agree to practice effective contraception
- •Willing and able to comply with scheduled visits, treatment plan, laboratory tests and other procedures
排除标准
- •Patients diagnosed with certain disease histologies including pediatric lymphomas/leukemias, monoclonal gammopathy of undetermined significance (MGUS), T-cell histiocyte large B cell lymphoma
- •Pregnant or lactating women
- •Active bacterial, viral, and fungal infections
- •History of allogeneic stem cell transplantation
- •Treatment with any prior lentiviral or retroviral based CAR-T
- •Patients receiving live (attenuated) vaccines within 4 weeks of screening visit or need for live vaccine on study
- •Patients with known active central nervous system (CNS) disease. Patients with prior CNS disease that has been effectively treated may be eligible
- •History of Class III or IV New York Heart Association (NYHA) heart failure, myocardial infarction, unstable angina or other significant cardiac disease within 6 months of screening
- •Involvement of cardiac tissue by lymphoma
- •Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura (ITP)
- •HIV-1 and HIV-2 antibody positive patients
结局指标
主要结局
Frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events
时间窗: 35 days
To determine the frequency, relatedness, severity and duration of treatment emergent and treatment related adverse events
Number of first cycle dose limiting toxicities (DLT) as assessed by Common Terminology Criteria for Adverse Events (CTCAE)
时间窗: up to 1 year
Based on the number of first cycle dose limiting toxicities (DLT) as assessed by CTCAE to determine maximum tolerated dose (MTD)
次要结局
- Area under the curve (AUC) of SWI019(up to Day 35)
- Maximum drug concentration (Cmax) of SWI019(up to Day 35)
- Time to reach Cmax (Tmax) of SWI019(up to Day 35)
- Clearance (CL) of SWI019(up to Day 35)
- Quantification of CLBR001 cells in peripheral blood(up to 1 year)
- Immunogenic response to CLBR001(up to 1 year)
- Overall survival (OS)(up to 1 year)
- Immunogenic response to SWI019(up to 1 year)
- Apparent elimination half-life (t1/2) of SWI019(up to Day 35)
- Phenotype of CLBR001 in peripheral blood and/or tumor/bone marrow biopsies(up to 1 year)
- Serum cytokine concentrations(up to 1 year)
- Overall (best) objective response by the Response Evaluation Criteria in Lymphoma (RECIL) and Lugano criteria(up to 1 year)
- Duration of response (DOR)(up to 1 year)
- Progression free survival (PFS)(up to 1 year)