PRIMARY OBJECTIVES:~I. To determine the efficacy measured by complete remission (CR) rate of the acalabrutinib in combination with rituximab in newly diagnosed elderly mantle cell lymphoma (MCL) patients.~II. To determine the safety profile of acalabrutinib with rituximab combination in elderly patients with MCL.~SECONDARY OBJECTIVES:~I. To evaluate the overall response (OR) rate. II. To evaluate the progression-free survival and overall survival. III. To assess serial minimal residual disease (MRD) using clonoseq, circulating tumor deoxyribonucleic acid (ct-DNA) based serial clonal evolution.~IV. Perform baseline genomic profiling for recognizing the predictive signature for response, serial MCL specific analytes assessments while on therapy.~EXPLORATORY OBJECTIVES:~I. Clonal evolution with targeted sequencing (seq) on ctDNA samples in sequential samples using a MCL specific customized gene panel would be assessed.~II. MRD assay using IgH clonoseq and ctDNA analysis, flow cytometry at various time points from peripheral blood (PB)/bone marrow (BM).~III. Sequential immunologic studies with cytokines/chemokines using a analyte panel, T cell numbers, and immunoglobulins (Ig).~IV. Tissue microenvironmental studies with simultaneous assessment of PB, BM and lymph nodes for gene expression profiling (GEP), single cell seq, ribonucleic acid (RNA) seq and clonal heterogeneity and the impact of acalabrutinib (A)-rituximab (R) treatment.~V. Extensive bioinformatics studies. VI. Identification of signaling pathways or biomarkers that predict sensitivity after therapy.~OUTLINE:~Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab intravenously (IV) over 3-4 hours on days 1, 8, 15, and 22 of cycle 1, and day 1 of cycles 2-12, 14, 16, 18, 20, 22 and 24. Cycles repeats every 28 days for up to 24 months or until complete remission is achieved in the absence of disease progression or unacceptable toxicity.~After completion of study intervention, patients are followed up at 30 days for 1 year, every 4 months for 2 years, every 6 months for 2 years, and then annually for 3 years.
This phase II trial studies the side effects of acalabrutinib and rituximab and its effect in treating patients with previously untreated mantle cell lymphoma. Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Rituximab is a monoclonal antibody that binds to a protein called CD20, which is found on B-cells, and may kill cancer cells. Giving acalabrutinib and rituximab may help to control mantle cell lymphoma in elderly patients.