A Study to Evaluate Acalabrutinib, in Combination With the R-CHOP Standard of Care, for Previously Untreated Mantle Cell Lymphoma in Spain

INCLUSION CRITERIA: 1. Adult men or women. 2. Pathologically confirmed MCL, with documentation of chromosome translocation t(11;14)(q13;q32) and/or overexpression of cyclin D1 in association with other relevant markers. 3. MCL requiring treatment and for which no prior systemic anticancer therapies have been received. 4. Unsuitable for autologous stem cell transplantation. 5. Presence of radiologically measurable lymphadenopathy, splenomegaly and/or extranodal lymphoid malignancy. 6. Eastern Cooperative Oncology Group (ECOG) performance status of ≤2. 7. Men who are sexually active and can beget children must agree to use highly effective forms of contraception during the study treatment and for 12 months after the last dose of rituximab or cyclophosphamide, 6 months after the last dose of doxorubicin, 30 days after the last dose of vincristine, and 2 days after the last dose of acalabrutinib, whichever is longest. 8. Men must agree to refrain from sperm donation during the study treatment and for 12 months after the last dose of rituximab or cyclophosphamide, 6 months after the last dose of doxorubicin, 30 days after the last dose of vincristine, and 2 days after the last dose of acalabrutinib, whichever is longest. 9. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing tablets without difficulty. 10. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations). 11. WOCBP who are sexually active must use highly effective methods of contraception during the study treatment and for 12 months after the last dose of rituximab or cyclophosphamide, 6 months after the last dose of doxorubicin, 30 days after the last dose of vincristine, and 2 days after the last dose of acalabrutinib, whichever is the longest. 12. Male patients should use barrier contraception from the time of screening until 12 months after the last dose of rituximab or cyclophosphamide, 6 months after the last dose of doxorubicin, 30 days after the last dose of vincristine, and 2 days after the last dose of acalabrutinib, whichever is longest. Male patients wishing to father children in the future should be advised to arrange for the freezing of sperm prior to the start of study treatment. EXCLUSION CRITERIA: 1. History of prior malignancy except for the following: 1. Malignancy treated with curative intent and with no evidence of active disease present for more than 2 years before screening and felt to be at low risk for recurrence by treating physician. 2. Adequately treated lentigo maligna melanoma without current evidence of disease or adequately controlled nonmelanomatous skin cancer. 3. Adequately treated carcinoma in situ without current evidence of disease. 2. Subjects for whom the goal of therapy is tumor debulking before stem cell transplant. 3. Subjects who are deemed by the treating physician to be unfit to tolerate the R-CHOP regimen. 4. Any history of central nervous system (CNS) lymphoma or leptomeningeal disease. 5. Uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP). 6. Major surgical procedure within 28 days before first dose of study drug. 7. Significant cardiovascular disease such as uncontrolled or untreated 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 at screening. Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study. 8. Absolute neutrophil count (ANC) \<1.0 x 109/L or platelet count \<75 x 109/L; for subjects with disease involvement in the bone marrow, ANC \<0.75 x 109/L or platelet count \<50 x 109/L. Subjects will only be considered eligible if peripheral blood counts can be maintained independent of growth factors or transfusions during the screening period. 9. Total bilirubin \>1.5 x upper limit normal (ULN) unless other reason known; or aspartate aminotransferase (AST) or alanine transaminase (ALT) \>2.5 x ULN. 10. Estimated creatinine clearance of \<30 mL/min, calculated using the formula of Cockcroft and Gault \[(140-age) • mass (kg)/(72 • creatinine mg/dL) • multiply by 0.85 if female\]. 11. Prothrombin time/international normalized ratio (INR) or activated partial thromboplastin time (aPTT) (in the absence of a lupus anticoagulant) \>2.0 x ULN. Exception: Subjects receiving a vitamin K antagonist are excluded; however, those receiving other anticoagulant therapy who have a higher INR/aPTT may be permitted to enroll to this study after discussion with the medical monitor. 12. 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. 13. Uncontrolled active systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment), or intravenous anti-infective treatment within 2 weeks before first dose of study drug. 14. Known history of infection with human immunodeficiency virus (HIV). 15. Ongoing immunosuppressive therapy, including systemic corticosteroids within 2 weeks before the first dose of study drug. 16. Known history of anaphylaxis or hypersensitivity to any study drug, or any of their components. 17. Serologic status reflecting active hepatitis B or C infection. 1. Subjects who are anti-HBc positive and who are surface antigen negative will need to have a negative