Acalabrutinib With Bendamustine / Rituximab Followed by Cytarabine / Rituximab for Untreated Mantle Cell Lymphoma

Inclusion Criteria

• Histologically confirmed mantle cell lymphoma with documented expression of Cyclin D1 by immune-histochemical stains and/or t(11;14) by cytogenetics or FISH.
• Presence of evaluable disease by PET imaging per the Lugano classification.
• Eligible for autologous stem cell transplantation.
• Between 18 and 70 years of age, inclusive.
• ECOG performance status ≤ 2
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1, 000/mcL unless, in the opinion of the treating physician, neutropenia is due to splenomegaly or bone marrow involvement
• Platelets ≥ 100, 000/mcL unless, in the opinion of the treating physician, thrombocytopenia is due to splenomegaly or bone marrow involvement
• Total bilirubin ≤ 2.0 x IULN and AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN except when, in the opinion of the treating physician, elevation is due to direct involvement of lymphoma (e.g. hepatic infiltration or biliary obstruction due to lymphoma) or Gilbert's disease
• Creatinine ≤ IULN OR creatinine clearance ≥ 40 mL/min for patients with creatinine levels above institutional normal
• Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control, abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she must inform her treating physician immediately.
• Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Exclusion Criteria

• Any previous chemotherapy or radiation for mantle cell lymphoma. Short course of steroids for symptom relief prior to presentation is permissible.
• Symptomatic meningeal or parenchymal brain lymphoma.
• Prior exposure to a BTK inhibitor.
• Currently receiving any other investigational agents.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to acalabrutinib, rituximab, cytarabine, bendamustine, or other agents used in the study.
• Received a live virus vaccination within 28 days of first dose of study drug.
• 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.
• Clinically 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. Exception: subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll on study.
• Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel 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.
• Active bleeding or history of bleeding diathesis (eg, hemophilia or von Willebrand disease).
• Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura).
• Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.
• Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of study drug.
• Prothrombin time (PT)/INR or aPTT (in the absence of lupus anticoagulant) >2x ULN. Exception: Subjects receiving warfarin are excluded; however, those receivi