A Phase 2 Study to Evaluate the Safety and Efficacy of Pacritinib in Relapsed or Refractory Waldenström Macroglobulinemia

Inclusion Criteria: * Age ≥18 years * ECOG performance status ≤2 * Clinicopathological diagnosis of Waldenström Macroglobulinemia * Symptomatic disease meeting criteria for treatment using consensus panel criteria from the Second International Workshop on Waldenström macroglobulinemia. At least one of the following: * constitutional symptoms: recurrent fever, night sweats, fatigue or weight loss * progressive or symptomatic lymphadenopathy or splenomegaly * hemoglobin ≤10 g/dL * platelet count ≤100 k/uL * hyperviscosity syndrome * symptomatic peripheral neuropathy * systemic amyloidosis * renal insufficiency * symptomatic cryoglobulinemia * Serum IgM level ≥ 2 times the upper limit of normal * Participants must meet the following organ and marrow functions as defined below: * absolute neutrophil count ≥0.5 k/uL without growth factor within 7 days * platelet count ≥50 k/uL without platelet transfusion within 7 days * total bilirubin ≤1.5 times the upper limit of normal or ≤3 times the upper limit of normal with documented liver involvement, hemolysis or Gilbert's disease * AST (SGOT) and ALT (SGPT) ≤2.5 times the upper limit of normal or ≤5 times the upper limit of normal with documented liver involvement * Creatinine clearance ≥30 ml/min using Cockcroft/Gault equation * Ability to understand and the willingness to sign a written informed consent document. (Providing consents in as many languages as possible is encouraged) * At least 2 prior lines of treatment for Waldenström Macroglobulinemia. Participants must either be BTK inhibitor exposed or not be a candidate for BTK therapy. * Women of childbearing potential: Females of childbearing potential (FCBP) will be required to use two highly effective forms of contraception simultaneously or will remain abstinent from heterosexual intercourse during the following periods related to this study: 1. while participating in the study; and 2) for at least three months (90 days) after discontinuation from the study. FCBP must be referred to a qualified provider of contraceptive methods if needed. Exclusion Criteria: * Current history of uncontrolled HIV * Patients with a known history of HIV must have a viral load assessed for eligibility and must be on a stable antiretroviral regimen that can be administered concurrent with pacritinib. * Known active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection based on criteria below * Hepatitis B virus (HBV): Patients with positive hepatitis B surface antigen (HBsAg) are excluded. Patients with positive hepatitis B core antibody (antiHBc) and negative HBsAg require hepatitis B polymerase chain reaction (PCR) evaluation before enrollment. Patients who are hepatitis B PCR positive will be excluded. * Hepatitis C virus (HCV): positive hepatitis C antibody. If positive hepatitis C antibody result, patient will need to have a negative result for hepatitis C ribonucleic acid (RNA) before enrollment. Patients who are hepatitis C RNA positive will be excluded. * Participants with chronic liver disease and hepatic impairment meeting Child-Pugh class B or C (Appendix B) * Participants who are pregnant, breast feeding, or planning to become pregnant while enrolled in this study or within 3 month after last study dose (2 weeks for breastfeeding) * Current CNS involvement by WM * Active alcohol or drug abuse * Concurrent administration of medications that are moderate or strong inhibitors or inducers of CYP3A within 14 days or 5 half-lives, whichever is shorter, prior to first dose of study drug. * Concurrent participation in another therapeutic clinical trial * History of another malignancy, except adequately treated local basal cell or squamous cell carcinoma of the skin, cervical carcinoma in situ, superficial bladder cancer, localized prostate cancer, or other adequately treated cancer currently in complete remission * Prior or ongoing clinically significant illness, including active infections requiring antibiotics, of medical condition that, in the investigator's opinion, could affect the safety of the patient; alter the absorption, distribution, metabolism or excretion of the study drug; or impair the assessment of study results * Inability to swallow pills * Significant cardiovascular disease defined as: * Unstable angina, or * History of myocardial infarction within 6 months prior to planned start * Previously documented left ventricular ejection fraction (LVEF) by any method of ≤ 45% in the 12 months prior to planned start; assessment of LVEF via echocardiogram or multigated acquisition (MUGA) scan during screening should be performed in selected patients as medically indicated, or * Any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification, or * Uncontrolled or symptomatic arrhythmias * Prolonged QT Interval with baseline QTc \>480 msec using the Bazette formula * Ongoing, active infection. * Active bleeding requiring blood transfusion or other medical intervention. Participants requiring anticoagulation therapy are not excluded.