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

Phase 2

Recruiting

Conditions: Diffuse large B-cell lymphoma
lymphoma
10025320

Registration Number: NL-OMON52540

Lead Sponsor: HOVO

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Recruiting

Sex: Not specified

Target Recruitment: 90

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
• 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

Exclusion Criteria

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

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary endpoint<br /><br>• Disease free survival measured from the date of registration to relapse or<br /><br>death from any cause whichever comes first. </p><br>

Secondary Outcome Measures

Name	Time	Method
<p>• (severe) adverse events and the relation of adverse events in time to<br /><br>recovery of the T-cell repertoire.<br /><br>• Overall survival, calculated from registration until death from any cause.<br /><br>• The relationship between MRD status at the end-of-induction and<br /><br>end-of-consolidation therapy.<br /><br>• The relation between MRD conversion and 2-years DFS and OS<br /><br>• The relationship between T-cell repertoire, PDL1/HLA expression, mutational<br /><br>load, gene immune signature, microbiome and effect of atezolizumab on MRD<br /><br>conversion.<br /><br>• The relation between the T-cell and NK cell repertoire and adverse events.</p><br>

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