Phase 3 randomized, double-blind, placebo-controlled, study assessing the efficacy and safety of acalabrutinib plus rituximab,cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) vs placebo plus R-CHOP in subjects ≤75 years of age with previously untreated non-germinal center diffuse large B-cell lymphoma.

Phase 3 randomized, double-blind, placebo-controlled, study to evaluate the efficacy and safety of acalabrutinib plus rituximab,cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as compared with placebo plus R-CHOP in subjects ≤75 years of age with previously untreated non-germinal center diffuse large B-cell lymphoma (activated B-cell (ABC) and unclassified).

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

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Participant Care provider Investigator Outcomes assessor