A Combination of Acalabrutinib With R-CHOP in Subjects With Previously Untreated Non-GCB DLBCL (ACE-LY-312)

Inclusion Criteria:

* Men and women, age ≥18 and ≤75 years
* Pathologically confirmed DLBCL, sufficient diagnostic material should be available to forward to a central laboratory for gene expression profiling and pathology review.
* No prior treatment for DLBCL
* Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
* International Prognostic Index (IPI) score of 1 to 5
* Disease Stage II to IV by the Ann Arbor Classification
* Adequate organ and marrow function
* Agreement to use highly effective forms of contraception during the study and 12 months after the last dose of rituximab

Exclusion Criteria:

* Evidence of severe or uncontrolled systemic diseases
* Known history of a bleeding diathesis (i.e., haemophilia, von Willebrand disease)
* History of stroke or intracranial haemorrhage in preceding 6 months.
* Known CNS lymphoma or leptomeningeal disease
* Known primary mediastinal lymphoma
* Known High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements
* Prior history of indolent lymphoma or CLL
* History of or ongoing confirmed PML
* Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of first dose of study drug, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
* Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach, extensive small bowel resection that is likely to affect absorption, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
* Uncontrolled active systemic fungal, bacterial, viral, or other infection
* Prior anthracycline use ≥150 mg/m2