Programmed death ligand 1 (PD-L1) PET imaging in patients with (Diffuse) Large B-cell Lymphoma who are treated with CD19-directed CAR T-cell therapy: a pilot study
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- to study the expression of PD-L1 in normal tissue and lymphoma lesions before CD19- directed CAR T-cell therapy in LBCL patients by 89Zr-atezolizumab PET/CT imaging and to correlate pretreatment 89Zr-atezolizumab uptake to response to CD19-directed CAR T-cell therapy and thereby identify clinically relevant PD-L1 expression. Heterogeneity of 89Zr-atezolizumab uptake will be evaluated by measuring standardized uptake value (SUV) on the 89Zr-atezolizumab PET/CT scan
研究概览
简要总结
To study the expression of PD-L1 in normal tissue and lymphoma lesions before CD19-directed CAR T-cell therapy in LBCL patients by 89Zr-atezolizumab PET/CT imaging and to correlate pretreatment 89Zr-atezolizumab uptake to the response to CD19-directed CAR T-cell therapy and thereby identify clinically relevant PD-L1 expression.
To study whether the amount of 89Zr-atezolizumab uptake, measured by the intensity of 89Zr-atezolizumab PET/CT imaging (SUV), can be used to differentiate lymphoma activity and treatment-related inflammatory signal (histiocytic/sarcoid-like reaction) in patients with an end-of-treatment 18F-FDG-positive PET/CT signal.
研究设计
- 分配方式
- Not Applicable
- 主要目的
- Single-arm
- 盲法
- None
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed DLBCL and associated subtypes, defined by WHO 2016 classification: DLBCL not otherwise specified (NOS), High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements with DLBCL histology (DHL/THL) and FL3B, Aggressive B-cell lymphoma, T-cell/histiocyte rich B-cell lymphoma, Primary mediastinal B-cell lymphoma, EBV+ DLBCL, transformed lymphoma (e.g. transformed follicular or marginal zone lymphoma)
- •Eligible for CAR T-cell therapy according to criteria set by the Dutch National Tumor Board
- •Measurable disease, as defined by Lugano criteria
- •Signed informed consent
- •Age ≥18 at the time of signing informed consent
- •Ability to comply with the protocol
排除标准
- •Signs or symptoms of active infection within 2 weeks prior to 89Zr-atezolizumab injection unless treated to resolution
- •History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- •Any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of 89Zr-atezolizumab, or that may affect the interpretation of the results or render the patient at high risk from complications
结局指标
主要结局
to study the expression of PD-L1 in normal tissue and lymphoma lesions before CD19- directed CAR T-cell therapy in LBCL patients by 89Zr-atezolizumab PET/CT imaging and to correlate pretreatment 89Zr-atezolizumab uptake to response to CD19-directed CAR T-cell therapy and thereby identify clinically relevant PD-L1 expression. Heterogeneity of 89Zr-atezolizumab uptake will be evaluated by measuring standardized uptake value (SUV) on the 89Zr-atezolizumab PET/CT scan
to study the expression of PD-L1 in normal tissue and lymphoma lesions before CD19- directed CAR T-cell therapy in LBCL patients by 89Zr-atezolizumab PET/CT imaging and to correlate pretreatment 89Zr-atezolizumab uptake to response to CD19-directed CAR T-cell therapy and thereby identify clinically relevant PD-L1 expression. Heterogeneity of 89Zr-atezolizumab uptake will be evaluated by measuring standardized uptake value (SUV) on the 89Zr-atezolizumab PET/CT scan
To study whether the amount of 89Zr-atezolizumab uptake, measured by the intensity of 89Zr-atezolizumab PET/CT imaging (SUV), can be used to differentiate between lymphoma activity and treatment-related inflammatory reaction (histiocytic/sarcoidlike reaction) in patients with an end-of-treatment 18F-FDG-positive PET/CT signal
To study whether the amount of 89Zr-atezolizumab uptake, measured by the intensity of 89Zr-atezolizumab PET/CT imaging (SUV), can be used to differentiate between lymphoma activity and treatment-related inflammatory reaction (histiocytic/sarcoidlike reaction) in patients with an end-of-treatment 18F-FDG-positive PET/CT signal
次要结局
- To correlate the pretreatment 89Zr-atezolizumab distribution to CAR T-cell peak expansion and persistence
- To correlate the pretreatment 89Zr-atezolizumab uptake to CAR T-cell therapy related grade 1-5 adverse events (cytokine release syndrome (CRS) and immune effector cell associated neurotoxicity syndrome (ICANS)).
- To correlate tumor 89Zr-atezolizumab uptake with tumor and immune cell PD-L1 expression as assessed by immunohistochemistry on a fresh contemporaneous tumor biopsy
- To compare the 89Zr-atezolizumab distribution in irradiated versus non-irradiated lymphoma lesions in patients who require radiotherapy as a bridging strategy prior to CAR T-cell infusion. If possible, these results will be compared to tumor and immune cell PD-L1 expression as assessed by immunohistochemistry on a fresh contemporaneous tumor biopsy of an irradiated lymphoma lesion
- To determine the incidence of a treatment-related inflammatory signal on 18F-FDGPET/CT scan (histiocytic/sarcoid-like reaction) after CAR T-cell therapy
研究者
Janneke de Boer
Scientific
Universitair Medisch Centrum Groningen