Acalabrutinib and Rituximab in Elderly Patients With Untreated Mantle Cell Lymphoma

Prior treatment

• Patients considered fit enough to undergo autologous or allogeneic stem cell transplant for MCL
• Major surgery within two weeks prior to day 1 of cycle 1
• Diagnosed with or treated for any other malignancy than MCL within 2 years prior to day 1 of cycle 1 (except basal cell carcinoma, cutaneous squamous cell carcinoma or any other in situ malignancy)
• Concurrent treatment with another investigational agent outside of this protocol
• The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study drug is prohibited
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug
• Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Patients receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study
• History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug
• Concurrent participation in another therapeutic clinical trial
• Received a live virus vaccination within 28 days of first dose of study drug

Other illness

• Patients who are unable to swallow capsules, or who have disease significantly affecting gastrointestinal function that would limit oral absorption of medication
• Known serological positivity for HBV, HCV, HIV. Patients who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result. Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Patients who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded
• Active infection requiring treatment
• Serious medical or psychiatric illness likely to interfere with participation in this clinical study
• Known history of drug-specific hypersensitivity or anaphylaxis to rituximab or acalabrutinib (including active product or excipient components).
• Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand disease)
• Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
• History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)
• Significant cardiovascular disease such as 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 at Screening. Note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study

Lab values

• Prothrombin time/INR or aPTT (in the absence of Lupus anticoagulant) \> 2x ULN

Other

• Breastfeeding or pregnant women

• Age ≥60 years
• Pathologically confirmed MCL (according to the 2016 WHO classification), with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1
• Stage II-IV, measurable by imaging and requiring treatment in the opinion of the treating clinician
• No previous treatment for MCL (other than localised radiotherapy or 7-day pulse of steroids for symptom control)
• ECOG performance status 0 - 2
• Absolute neutrophil count (ANC) \> 1.0 x 109 and platelet count \>100 x 109, unless related to lymphoma - in this situation, the threshold for inclusion is ANC \> 0.5 x 109 and platelet count \> 50 x 109
• Creatinine clearance \> 30 ml/min (Cockcroft-Gault)
• AST and/or ALT \<3xULN and/or total bilirubin \<3xULN
• Able to give voluntary written informed consent
• Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and for 2 days after the last dose of acalabrutinib or for 12 months after last dose of rituximab, whichever is longer