Phase II Study of Pacritinib in Kaposi Sarcoma Herpesvirus (KSHV)-Associated Multicentric Castleman Disease and KSHV-Associated Inflammatory Cytokine Syndrome (KICS)

Inclusion Criteria

• - INCLUSION CRITERIA: - Participants must meet KSHV-associated Inflammatory Cytokine Syndrome (KICS) criteria or have histologically or cytologically confirmed Kaposi sarcoma herpesvirus -multicentric Castleman disease (KSHV-MCD) confirmed by the CCR, Laboratory of Pathology (LP), NCI - Age >= 18 years - At least one clinical symptom attributed to KSHV-MCD or KICS, as follows: - Intermittent or persistent fever for at least 1 week (>38 degrees C) - Fatigue (CTCAE - Grade >=2) - Gastrointestinal symptoms (e.g., nausea and anorexia - CTCAE Grade >=1) - Respiratory symptoms (e.g., cough and airway hyperreactivity - CTCAE Grade >=1) - At least one laboratory abnormality attributed to KSHV-MCD or KICS, as follows: - Anemia (hemoglobin [Hgb] 7.0 - 12.5gm/dL) - Thrombocytopenia (50,000 - 150,000/mm3) - Hypoalbuminemia (<3.4 g/dL) - Elevated C-reactive protein [CRP] (>3mg/L) - No life or organ-threatening manifestations of KSHV-MCD, KICS or Kaposi Sarcoma (KS) - Eastern Cooperative Oncology Group [ECOG] performance status <= 3 (Karnofsky >=60%) - Participants must have laboratory parameters as defined below: - Total bilirubin <=3 X upper limit of normal (ULN) or <6X ULN for diagnosis of Gilbert's - AST(SGOT)/ALT(SGPT) <=2.5 X ULN - PT/PTT/INR <=1.5 X ULN - Creatinine within normal institutional limits OR Creatinine clearance >=30mL/min/1.73 m^2 as estimated by either Cockcroft-Gault or 24-hour urine collection for participants with creatinine levels above ULN - Participants with HIV should be receiving and willing to continue or willing to initiate an effective antiretroviral therapy (ART) regimen that excludes strong/ moderate CYP3A4 inducer or inhibitors. - For participants with evidence of chronic hepatitis B virus (HBV) infection, participants must be on suppressive therapy. - Participants with a history hepatitis C virus (HCV) infection must have completed treatment with evidence of sustained virologic response for a period of at least 3 months. - Participants with KSHV-MCD (Cohort 2) or KICS (Cohort 3) who have received prior therapy, such as rituximab or other monoclonal antibodies, must have a wash out period of at least 3 weeks. - Participants receiving medications or substances that are substitutes of strong CYP3A4 inhibitors must have a washout period of at least 5 half-lives of the drug prior to enrollment on study. - Individuals of child-bearing potential (IOCBP) must agree to use a highly effective method of contraception (e.g., intrauterine device [IUD], hormonal [excluding hormonal contraceptives sensitive to CYP3A4 metabolism (i.e. progestin)], surgical sterilization, abstinence) prior to study entry, for the duration of study participation, and for up to 30 days after discontinuation of the study drug. - Individuals able to father a child with a partner able to become pregnant must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) for the duration of the study treatment and up to 30 days after the last dose of the study drug. - Ability of participant to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: - Grade >2 symptomatic visceral KS (except for edema or non-ulcerating disease restricted to the oral cavity). - History of allergic reactions attributed to compounds of similar chemical or biologic composition to pacritinib. - Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4. Lists including medications and substances known or with the potential to interact with the specified CYP3A4 isoenzymes. - Participants with evidence of ongoing hemorrhage, active signs/symptoms of bleeding, or history of severe bleeding complications in the one year prior to enrollment. - Any history of CTCAE grade >= 3 cardiac events within the last 3 months. - QTc(Fredericia) prolongation >480 ms or other factors that increase the risk for QTc prolongation (i.e., heart failure, or a history of long QT interval syndrome). - Use of concomitant medications with significant potential for QTc prolongation - History of thrombosis, troponin-positive (Tpos) or myocardial infarction within the last 6 months - Participants with moderate (Child-Pugh Score B) or severe hepatic impairment (Child-Pugh Score C) - Diagnosis of primary effusion lymphoma [PEL] or another lymphoma. - Participants with a prior or concurrent malignancy whose natural history or treatment that has potential to interfere with the safety or efficacy assessment of the regimen. - Pregnant individuals as evaluated by a positive serum or urine beta-hCG at screening. - There is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the nursing person with pacritinib. Breastfeeding should be discontinued if the nursing person is treated with pacritinib. - Uncontrolled bacterial, mycobacterial, or fungal infection at screening. - Uncontrolled intercurrent illness that would limit compliance with study requirements, including results of hematology and chemistry testing, infection disease (etc.)