Modified VR-CAP and Acalabrutinib as First Line Therapy for the Treatment of Transplant-Eligible Patients With Mantle Cell Lymphoma

Inclusion Criteria:

• Age 18-75 years
• No prior therapy for mantle cell lymphoma (MCL)
• MCL in need of systemic therapy, and potentially eligible for ASCT as assessed by thetreating physician
• Documented histological confirmation of MCL by local institutional review
• Documented, fludeoxyglucose F-18 (FDG)-avid measurable disease (at least 1 lesion >= 1.5 cm in diameter) as detected by positron emission tomography (PET)/computedtomography (CT) and as defined and includes measurable nodal and extranodal diseasesites, or splenomegaly measuring more than 13 cm in vertical length
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1, 2
• Absolute neutrophil count (ANC) >= 1000/mm^3 or >= 500/mm^3 if due to lymphomatousmarrow or spleen involvement (obtained =< 30 days prior to registration)
• Platelet count >= 100,000/mm^3 or >= 75,000/mm^3 if due to lymphomatous marrow orspleen involvement (obtained =< 30 days prior to registration)
• Total bilirubin =< 1.5 x upper limit of normal (ULN) (unless documented Gilbert'ssyndrome, for which total bilirubin =< 3 x upper limit of normal [ULN] is permitted) (obtained =< 30 days prior to registration)
• Aspartate transaminase (AST) =< 3 x ULN (obtained =< 30 days prior to registration)
• Prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastintime (PTT) =< 2 x ULN, unless elevated due to a lupus anticoagulant (obtained =< 30days prior to registration)
• Calculated creatinine clearance must be >= 30 ml/min using the Cockcroft-Gault formula (obtained =< 30 days prior to registration)
• Negative pregnancy test done within =< 14 days prior to registration for women ofchildbearing potential only
• For women of childbearing potential (WOCBP, defined as premenopausal women capable ofbecoming pregnant): Must agree to use of highly effective method of birth controlduring study therapy and until 12 months after last dose of study therapy. NOTE: 'Acceptable' methods are not adequate. Highly effective methods are defined byClinical Trials Facilitation and Coordination Group [CTFG] as having a failure rate of < 1% per year
• Men must agree to use barrier contraception starting with the first dose of studytherapy and through 180 days after completion of study therapy
• Provide informed written consent
• Willing to return to enrolling institution for follow-up (during the Active MonitoringPhase of the study)
• Hematologic labs must be obtained within =< 14 days of registration
• Willing and able to participate in all required evaluations and procedures in thisstudy protocol
• Ability to understand the purpose and risks of the study and provide signed and datedinformed consent and authorization to use protected health information

Exclusion Criteria:

• Prior systemic treatment for mantle cell lymphoma. Short course of steroids (=< 7days) for symptom management or localized radiation is permissible, as long asmeasurable disease outside of the radiation field exists
• Peripheral neuropathy or neuropathic pain of grade 2 or worse as assessed by theinvestigator
• Prior exposure to bortezomib or a BTK inhibitor
• Prior anthracycline exposure unless cumulative prior exposure is under 150 mg persquare meter
• Requiring anticoagulation with warfarin or equivalent vitamin k antagonist
• Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopeniapurpura)
• Active bleeding or history of bleeding diathesis (e.g. hemophilia or von Willebranddisease)
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment
• Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer
• Requiring treatment with a proton pump inhibitor. Examples include: dexlansoprazole,esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole, or therapeuticclass equivalents
• Note: H2-receptor agonists are not exclusionary
• History of allergic reactions attributed to acalabrutinib, cytarabine, bortezomib,boron, or any of the other agents administered as part of the therapeutic regimen inthis study
• Active systemic fungal, bacterial, viral, or other infection that is worsening (defined as increasing signs/symptoms of infection during screening) or, requiresintravenous antibiotic therapy
• Active or chronic uncontrolled hepatitis B or hepatitis C infection. Patients withpositive hepatitis B core antibody positive require negative polymerase chain reaction (PCR) prior to enrollment. Hepatitis B surface antigen positive or PCR positivepatients will be excluded. Patients with hepatitis C must have negative hepatitis Cvirus (HCV) ribonucleic acid (RNA) for inclusion
• Co-morbid systemic illnesses or other severe concurrent disease (including majorsurgery within 2 weeks) which, in the judgment of the investigator, would make thepatient inappropriate for entry into this study or interfere significantly with theproper assessment of safety and toxicity of the prescribed regimens
• Known to be human immunodeficiency virus (HIV) positive since antiretroviral therapyhas a potential for drug interactions with acalabrutinib
• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure or low cardiac ejection fraction (NewYork Heart Association [NYHA] class 3-4 or ejection fraction [EF] < 45%), unstableangina pectoris, cardiac arrhythmia, or psychiatric illness/social situations thatwould limit compliance with study requirements
• Receiving any other investigational agent which would be considered as a treatment forthe primary neoplasm
• Other active malignancy =< 2 years prior to registration. EXCEPTIONS: Non-melanoticskin cancer localized prostate cancer, or carcinoma-in-situ of the breast or cervix.NOTE: If there is a history or prior malignancy, patients must not be receiving otherspecific treatment for their cancer
• Pregnant and/or breastfeeding
• Has difficulty with or is unable to swallow oral medication, or has significantgastrointestinal disease that would limit absorption of oral medication
• Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months beforescreening. unless directly due to MCL Involvement by endoscopic or histologicevaluation
• Major surgical procedure within 28 days of first dose of study drug. NOTE: If asubject had major surgery, they must have recovered adequately from any toxicityand/or complications from the intervention before the first dose of study drug
• Concurrent participation in another therapeutic clinical trial