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

This is a single-arm, open-label, multicenter, non-indication seeking phase II trial to describe the efficacy and safety of patients with mantle cell lymphoma (MCL) receiving acalabrutinib in combination with R-CHOP for the front-line treatment of MCL in Spain. Acalabrutinib will be administered until disease progression if medically appropriate, along with R-CHOP based on institutional standards. After 6 cycles of acalabrutinib in combination with R-CHOP, subjects who tolerate treatment and not progressing, will then receive monotherapy acalabrutinib. In addition, subjects who achieve a response (PR or greater) will receive maintenance rituximab every other 28-day cycle for a maximum of 12 additional doses. Thereafter, subjects receive monotherapy acalabrutinib until disease progression or treatment discontinuation.

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) \