|Exclusion Criteria:||1) History of disallowed therapies - Prior treatment with a BTK inhibitor - Prior extended radiotherapy for lymphoma (extended field radiotherapy such as mantle field radiation and inverted Y field radiation) - More than 150 mg/m2 of prior doxorubicin|
2) Prior multidrug chemotherapy for lymphoma. During dose-escalation, subjects with prior single-agent rituximab treatment, single-agent targeted therapy, or involved field radiation therapy is allowed. Short course (maximum of 10 days; not exceeding 100 mg/day) prednisone or equivalent steroids are allowed to treat symptoms in subjects with advanced disease who entered the screening phase and are waiting to be treated. Subjects who enter the expansion cohort are not permitted to have any prior antilymphoma treatment.
3) History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug
4) Major surgery within 3 weeks before enrollment
5) Known bleeding diatheses or platelet dysfunction disorders or requires therapeutic anticoagulation (Vitamin K antagonists [warfarin, phenprocoumon], aspirin, low molecular weight heparin [LMWH], or other anticoagulants)
6) Known Central Nervous System (CNS) lymphoma
7) Women who are pregnant or breast-feeding, or planning to become pregnant within 12 months and males who plan to father a child while enrolled in this study or within 3 months after the last dose of study drug
8) Uncontrolled or severe cardiovascular disease, including myocardial infarction within 6 months of enrollment, New York Heart Association Class III or IV heart failure, uncontrolled angina, pericardial disease, cardiac amyloidosis, clinically significant cardiac arrhythmia, or left ventricular ejection fraction (LVEF) outside of institutional limits
9) Active systemic infection requiring treatment including hepatitis B and hepatitis C infection
10) Documented or suspected human immunodeficiency virus (HIV)/AIDS
11) Known allergies, hypersensitivity, or intolerance to cyclophosphamide, rituximab, prednisone, doxorubicin, vincristine, or its excipients
12) Diagnosed or treated for a malignancy other than NHL except; adequately treated non-melanoma skin cancer, curatively treated in situ cancer of the cervix, ductal carcinoma in situ of the breast, or other solid tumors curatively treated with no evidence of disease for > 5 years
13) Any condition that could interfere with the absorption or metabolism of ibrutinib including unable to swallow capsules, malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
14) Serious medical condition, such as active peptic ulcer disease, uncontrolled diabetes, or psychiatric illness, likely to interfere with participation in this clinical study
15) Concurrent treatment with another investigational agent. Concurrent participation in non-treatment studies is not excluded.
16) Any condition that, in the opinion of the investigator, would compromise the well-being) of the subject or the study or prevent the subject from meeting or performing study requirements
17) NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. If a subject's status changes (including laboratory results or receipt of additional medical records) after screening but before the first dose of study drug is given, such that he or she no longer meets all eligibility criteria, then the subject should be excluded from participation in the study.