Diffuse large B-cell Lymphoma MedDRA version: 20.0 Level: HLT Classification code 10012819 Term: Diffuse large B-cell lymphomas System Organ Class: 100000004851 MedDRA version: 20.0 Level: PT Classification code 10012818 Term: Diffuse large B-cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl
Conditions
Interventions
Product Name: 89ZR-N-SUCDF-ATEZOLIZUMAB
Product Code: 89ZR-N-SUCDF-MPDL3280A
Pharmaceutical Form: Solution for injection
INN or Proposed INN: ATEZOLIZUM
Sponsors
HOVON Foundation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: In order to receive information on the dynamics induced by R-CHOP, patients should preferably be included before standard R-CHOP therapy (at Part A). Alternatively, patients who are eligible can also be included after having achieved complete remission with standard R-CHOP therapy (i.e. at Part B). Inclusion criteria • Age 18-75 (inclusive) years • Patients with a confirmed histologic diagnosis of diffuse large B-cell lymphoma (DLBCL-NOS) based upon a representative histology specimen according to the WHO classification, revision 2016 (see appendix A) • Ann Arbor stages II-IV (see appendix B) • WHO performance status 0 – 1 (see appendix E) • IPI = 3 at diagnosis (see appendix C) • Negative pregnancy test at study entry • Patient is willing and able use adequate contraception during and until 5 months after the last protocol treatment. • Written informed consent • Patient is capable of giving a written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 10 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Diagnosis • All histopathological diagnoses other than DLBCL-NOS according to the WHO classification, revision 2016 (see appendix A), including: - High-grade B-cell lymphoma, with MYC and BCL2 and/or BCL6 translocations - Testicular large B-cell lymphoma - Primary mediastinal B cell lymphoma - Transformed indolent lymphoma - Post-transplant lymphoproliferative disorder Organ dysfunction • Clinical signs of severe pulmonary dysfunction • Clinical signs of heart failure (NYHA classification II-IV) • Symptomatic coronary artery disease or cardiac arrhythmias not well controlled with medication. • Myocardial infarction during the last 6 months • Significant renal dysfunction (serum creatinine = 150 umol/l or clearance = 30ml/min Creatinine clearance may be calculated by Cockcroft –Gault formula: CrCl = (140 - age [in years]) x weight [kg] (x 0.85 for females) / (0.815 x serum creatinine [µmol/L]) • Inadequate hematological function: hemoglobin 1.5, aPTT >33 • Significant hepatic dysfunction (total bilirubin = 1.5x upper limit of normal (ULN) or transaminases = 2.5 x ULN), unless related to Gilberts syndrome. • Clinical signs of severe cerebral dysfunction • Patients with a history of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant and adversely affecting compliance to study drugs • Major surgery within the last 4 weeks Known or suspected infection • Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection or any major episode of infection requiring treatment with IV antibiotics or hospitalization within 4 weeks before date of registration. Suspected active or latent tuberculosis needs to be confirmed by positive interferon gamma (IFN-?) release assay • Patients known to be HIV-positive • Active chronic hepatitis B or C infection • Administration of a live, attenuated vaccine within 4 weeks before date of registration or anticipation that such a live attenuated vaccine will be required during the study and for a period of 5 months after discontinuation of atezolizumab. Auto-immune • Any active or history of documented autoimmune disease, including but not limited to 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. The following exceptions are allowed: Patients with autoimmune-related hypothyroidism or type 1 diabetes mellitus who are on stable treatment. • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidenc
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate biodistribution of 89Zr-atezolizumab in patients with high risk DLBCL at diagnosis.;Primary end point(s): • Description of 89Zr-atezolizumab biodistribution in DLBCL by measuring standardized uptake value (SUV) on the 89Zr-atezolizumab-PET scans;Timepoint(s) of evaluation of this end point: Data analysis will be performed on an ongoing basis after every patient; Secondary Objective: • Assess the heterogeneity of 89Zr-atezolizumab tumor uptake in high-risk DLBCL before R-CHOP • Correlate 89Zr-atezolizumab biodistribution with PD-L1 expression on tumor cells and cells in the micro-environment as assessed by immunohistochemistry on archival tumor biopsies, soluble PD-L1 measurements and PD-L1 RNA expression • Evaluate 89Zr-atezolizumab biodistribution in metabolic complete remission following R-CHOP and assess the relation with minimal residual disease • Assess the 89Zr-atezolizumab biodistribution at relapse after treatment with atezolizumab for patients treated in the HOVON 151 trial • Correlate 89Zr-atezolizumab tumor uptake dynamics and biodistribution to potential adverse reactions of atezolizumab treatment for patients treated in the HOVON 151 trial • Establish the baseline characteristics for the T-cell and NK-cell repertoire and dynamics induced by R-CHOP • Establish the baseline characteristics for the microbiome and the dynamics induced by R-CHOP | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Tumor and immune cell PD-L1 expression analysis in an archival pre-treatment biopsy, will be correlated to 89Zr-atezolizumab tumor uptake, evaluated by measuring standardized uptake value (SUV) on the 89Zr-atezolizumab-PET • Correlation analysis of tumor 89Zr-atezolizumab uptake, evaluated by measuring standardized uptake value (SUV) and sPD-L1 levels in patient serum, assessed using ELISA • Correlation analysis of tumor 89Zr-atezolizumab uptake, evaluated by assessing immune signature by GEP • Correlation analysis of 89Zr-atezolizumab uptake and MRD status • Correlation analysis between 89Zr-atezolizumab off-target uptake and atezolizumab toxicity • Analysis of predictive value of 89Zr-atezolizumab imaging in high-risk DLBCL patients Exploratory study endpoints: • Establish baseline characteristics and dynamics for T-cell repertoire and microbiome after R-CHOP ;Timepoint(s) of evaluation of this end point: Data analysis will be performed on an ongoing basis after every patient | — |
Countries
Netherlands
Contacts
Public ContactHOVON Data Center (EE2155)
Erasmus MC, HOVON Data Center
Outcome results
None listed