Pacritinib in Combination With a BTK Inhibitor for the Treatment of Patients With Relapsed or Refractory Mantle Cell Lymphoma

PRIMARY OBJECTIVE: I. Obtain a preliminary estimate of the safety and tolerability of the combination of pacritinib with a covalent BTK inhibitor (e.g., ibrutinib, acalabrutinib, zanubrutinib) in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). SECONDARY OBJECTIVES: I. Obtain a preliminary estimate of the overall response rate (ORR) of the combination of pacritinib with a BTK inhibitor in patients with R/R MCL. II. Obtain a preliminary estimate of the duration of response and progression-free survival in patients with R/R MCL treated with a combination of pacritinib with a BTK inhibitor. EXPLORATORY OBJECTIVES: I. Explore the association between clinical outcomes, elimination of tumor associated macrophages (TAMs), and expression of IL-10. II. Evaluate minimal residual disease (MRD) in patients who obtain a complete metabolic response to therapy. OUTLINE: Patients receive pacritinib orally (PO) twice daily (BID) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also continue to receive BTK inhibitor per standard of care. Additionally, patients undergo blood sample collection, optional tissue biopsy, bone marrow biopsy and aspiration and positron emission tomography (PET)/computed tomography (CT) throughout the study. After completion of study treatment, patients are followed up at 30 days. Patients without progression are followed up every 3 months.