Ibrutinib and Standard Immuno-Chemotherapy in Younger, High-Risk Patients With Diffuse Large B-Cell Lymphoma

Exclusion Criteria

• •1. Vaccinated with live, attenuated vaccines within 4 weeks of inclusion.
• •2. Major surgery within 4 weeks of inclusion.
• •3. Any prior lymphoma-directed therapy (except pre-phase treatment).
• •4. Known central nervous system involvement.
• •5. Diagnosed or treated for malignancy other than diffuse large B-cell lymphoma, in particular any other (indolent) lymphoma.
• •6. Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 or 4 cardiac disease as defined by the New York Heart Association Functional classification.
• •7. Bone marrow involvement \> 25%
• •8. History of stroke or intracranial hemorrhage within six months of inclusion.
• •9. Requires anticoagulation with warfarin or equivalent vitamin K antagonist.
• •10. Known history of human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring IV antibiotics.
• •11. Requires treatment with strong CYP3A inhibitors.
• •12. Use of preparations containing St. John's Wort.
• •13. Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk.
• •14. Concurrent treatment with other investigational agent or X-ray therapy.
• •15. Previous chemo- or radiotherapy for any other malignancy, in particular indolent lymphoma.
• •16. Any psychological, cognitive, familial, sociological or geographical condition that, in the investigator's opinion, compromises the patient's ability to understand the patient information, to give informed consent or to comply with the study protocol.
• •17. Participation in another interventional clinical trial during this trial. There may be exceptions at the discretion of the coordinating investigator.