Atezolizumab for Diffuse large B-cell lymphoma

Inclusion criteria

• {"criterion_text":"- 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)\n- Eligible for CAR T-cell therapy according to criteria set by the Dutch National Tumor Board\n- Measurable disease, as defined by Lugano criteria\n- Signed informed consent\n- Age ≥18 at the time of signing informed consent\n- Ability to comply with the protocol"}

Exclusion criteria

• {"criterion_text":"- Signs or symptoms of active infection within 2 weeks prior to 89Zr-atezolizumab injection unless treated to resolution\n- History of severe allergic, anaphylactic or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins\n- 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"}

Primary endpoints

• {"endpoint_text":"- 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","definition_or_measurement_approach":"Heterogeneity of 89Zr-atezolizumab uptake will be evaluated by measuring standardized uptake value (SUV) on the 89Zr-atezolizumab PET/CT scan"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Amount of 89Zr-atezolizumab uptake measured by intensity on 89Zr-atezolizumab PET/CT imaging expressed as SUV to differentiate lymphoma activity vs treatment-related inflammatory reaction"}

Secondary endpoints

• {"endpoint_text":"- To correlate the pretreatment 89Zr-atezolizumab distribution to CAR T-cell peak expansion and persistence","definition_or_measurement_approach":"Correlation between pretreatment 89Zr-atezolizumab distribution (PET/CT uptake patterns) and CAR T-cell peak expansion and persistence (measured by CAR T-cell counts/expansion metrics)"}
• {"endpoint_text":"- 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)).","definition_or_measurement_approach":"Correlation between pretreatment PET tracer uptake and incidence/severity (grade 1-5) of CRS and ICANS events"}
• {"endpoint_text":"- To correlate tumor 89Zr-atezolizumab uptake with tumor and immune cell PD-L1 expression as assessed by immunohistochemistry on a fresh contemporaneous tumor biopsy","definition_or_measurement_approach":"Comparison of PET uptake in tumor lesions with PD-L1 expression measured by immunohistochemistry on contemporaneous tumor biopsy"}
• {"endpoint_text":"- 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","definition_or_measurement_approach":"Comparison of PET tracer distribution between irradiated and non-irradiated lesions; optionally compared to PD-L1 IHC on biopsy of irradiated lesion"}
• {"endpoint_text":"- To determine the incidence of a treatment-related inflammatory signal on 18F-FDGPET/CT scan (histiocytic/sarcoid-like reaction) after CAR T-cell therapy","definition_or_measurement_approach":"Incidence of histiocytic/sarcoid-like inflammatory signal on 18F-FDG PET/CT after CAR T-cell therapy"}

Netherlands

Earliest CTIS Part Ii Submission Date

15-11-2024

Latest Decision Or Authorization Date

20-11-2024

Processing Time Days

5

Number Of Sites

1

Number Of Participants

20

Primary sponsor

Full Name

Universitair Medisch Centrum Groningen

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands