A Combination of Acalabrutinib With R-CHOP for Patient Diffuse Large B-cell Lymphoma (DLBCL)

Inclusion Criteria: * Histologically confirmed DLBCL, expressing CD20. Sufficient diagnostic material should be available to forward to a central laboratory for gene expression profiling and pathology review. * Measurable disease of at least 15mm. * Not previously treated for lymphoma and fit enough to receive combination chemoimmunotherapy with curative intent. * Stage IAX (bulk defined as lymph node diameter \>10cm) to stage IV disease and deemed to require a full course of chemotherapy. Patients with non-bulky IE disease will not be eligible. * ECOG performance status 0-2 or 3 if this is directly attributable to lymphoma. * Adequate bone marrow function with platelets \> 100x109/L; neutrophils \> 1.0x109/L at study entry, unless lower figures are attributable to lymphoma. * Measured or calculated creatinine clearance \> 30mls/min, (calculated using the formula of Cockcroft and Gault \[(140-Age) x Mass (kg) x (1.04 (for women) or 1.23 (for men))/Serum Creatinine (µmolL)\]. * Serum bilirubin \< 35μmol/L and transaminases \< 2.5x upper limit of normal at time of study entry * Cardiac function sufficient to tolerate 300mg/m2 of doxorubicin. A pre-treatment echocardiogram or MUGA is required to establish baseline LVEF equal to or greater than 55%. * No concurrent uncontrolled medical condition. * Life expectancy \> 3 months. * Aged 16 years or above. * Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty. * Ability to understand the purpose and risks of the study and provide signed and dated informed consent. Exclusion Criteria: Patients will be excluded from the study entry if any of the following criteria are met: * Previous history of treated or untreated indolent lymphoma. However newly diagnosed patients with DLBCL who are found to also have small cell infiltration of the bone marrow or other diagnostic material (discordant lymphoma) will be eligible. * Patients who have received immunisation with a live vaccine within four weeks prior to enrolment will be ineligible. * Diagnosis of primary mediastinal lymphoma. * Diagnosis of primary Central Nervous System lymphoma. * History of stroke or intracranial haemorrhage in preceding 6 months. * History of bleeding diathesis (eg, haemophilia, von Willebrand disease). * Requires or receiving anticoagulation with warfarin or equivalent antagonists (eg, phenprocoumon) within 7 days of first dose of acalabrutinib. However patients using therapeutic low molecule weight heparin or low dose aspirin will be eligible. * Prior exposure to a BCR inhibitor (eg, Btk inhibitors, phosphoinositide-3 kinase (PI3K), or Syk inhibitors) or BCL-2 inhibitor (eg, ABT-199) * Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer. * Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Patients receiving proton pump inhibitors who switch to short-acting H2-receptor antagonists or antacids are eligible for enrolment into this study. * Uncontrolled systemic infection. * Major surgery in the preceding 4 weeks of first dose of study drug. If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug. * 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, or corrected QT interval (QTc) \> 480 msec at screening. * Serological positivity for Hepatitis B, C, or known HIV infection. As per standard of care, prior to initiation of immunochemotherapy, the results of hepatitis serology should be known prior to commencement of therapy. * Positive test results for chronic HBV infection (defined as positive HBsAg serology) will not be eligible. Patients with occult or prior HBV infection (defined as negative HBsAg and positive total HBcAb) will not be eligible. Patients who have protective titres of hepatitis B surface antibody (HBsAb) after vaccination will be eligible. * Positive test results for hepatitis C (HCV antibody serology testing) will not be eligible. * Women who are sexually active and can bear children must agree to use highly effective forms of contraception or abstinence during the study and for 12 months after the last treatment dose. Highly effective forms of contraception are defined in Section 4.7. * Breastfeeding or pregnant women. * Men who are sexually active and can father children must agree to use highly effective forms of contraception or abstinence during the study and for 12 months after the last treatment dose. Highly effective forms of contraception are defined in Section 4.7. * Men must agree to refrain from sperm donation during the study and for 12 months after the last treatment dose. * Serious medical or psychiatric illness likely to affect participation or that may compromise the ability to give informed consent. * Prior malignancy (other than DLBCL), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to \< 2 years. Note: these cases must be discussed with SCTU. * Malabsorption syndrome, disease significantly affecting gastrointestinal function, resection of the stomach or small bowel, gastric bypass, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction or gastric restrictions and bariatric surgery, such as gastric bypass. * Any immunotherapy within 4 weeks of 1st dose of the study. * Concurrent participation in another therapeutic clinical trial.