A phase II study evaluating the feasibility and clinical efficacy of atezolizumab consolidation treatment in high risk diffuse large B-cell lymphoma

• 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
• Ann Arbor stages II-IV
• WHO performance status 0 - 1
• IPI >=3 at diagnosis
• Complete metabolic remission (Deauville 1-3) after 6-8 cycles of R-CHOP
according to the Lugano criteria
• Negative pregnancy test at study entry
• Patient is willing and able to use adequate contraception during and until 5
months after the last protocol treatment.
• Written informed consent
• Patient is capable of giving informed consent

DIAGNOSIS
• All histopathological diagnoses other than DLBCL-NOS according to the WHO
classification, revision 2016 including:
- High-grade B-cell lymphoma with a double/triple translocation with MYC, BCL2
and/or BCL6. Please note that patients with an isolated MYC translocation or an
isolated BCL2 translocation or an isolated BCL-6 translocation are eligible
(single hit translocation).
- 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:
• Inadequate hematological function: hemoglobin 5.5 < mmol/L, ANC < 1.0x109/L
or platelets < 75x109 /L
• Signs or know history of bleeding disorder
• 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-γ) 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
regsitration 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
evidence of active pneumonitis per chest CT scan at screening.
• Patients with uncontrolled asthma or allergy, requiring systemic steroid
treatment
• Regular treatment with corticosteroids within the 4 weeks prior to date of
registration, unless administered for indications other than NHL at a dose
equivalent to < 30 mg/day prednisone/prednisolone.
GENERAL
• Serious underlying medical conditions, which could impair the ability of the
patient to participate in the trial (e.g. ongoing infection, uncontrolled
diabetes mellitus, gastric ulcers, active autoimmune disease).
• Current participation in another clinical trial interfering with this trial
• History of active cancer during the past 5 years, except basal cell carcinoma
of the skin, stage 0 cervical carcinoma or cracinoma in situ (for which no
systemic treatment was indicated)
• Life expectancy < 6 months .
• Any psychological, familial, sociological and geographical condition
potentially hampering compliance with the study protocol and follow-up
schedule, PRIOR TREATMENT.
• Prior treatment with atezolizumab, or anti PD-1 or PDL-1 antibodies.
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies,
including anti-CTLA4 therapeutic antibodies.
• Treatment with systemic immunostimulatory agents (including but not limited
to IFN, interleukin [IL]-2) within 6 weeks or 5 half-lives of the drug,
whichever is shorter, prior to date of registration.
• Treatment with systemic immunosuppressive medications, including but not
limited to prednisone, cyclophosphamide, azathioprine, methotrexate,
thalidomide, and anti-tumor necrosis factor (anti-TNF) agents within 2 weeks
prior to date of registration; inhaled corticosteroids and mineralocorticoids
are allowed.