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

Background: Kaposi sarcoma herpesvirus (KSHV)-associated inflammatory cytokine syndrome (KICS) and KSHV-multicentric Castleman disease (MCD) occur in people living with HIV. These diseases cause severe inflammation that can be fatal if not treated. Objective: To test a drug (pacritinib) in people with KSHV-associated KICS or MCD. Eligibility: People aged 18 years and older with KSHV-associated KICS or MCD. They must have at least one symptom. Design: Participants will be screened. They will have a physical exam with blood tests and tests of their heart function. They will have imaging scans. Their ability to perform everyday tasks will be reviewed. In some participants who have Kaposi sarcoma (KS) with KICS or MCD, these individuals may need a bronchoscopy and/or endoscopy of the upper or lower intestine: A flexible tube with a camera and a light source will be inserted through the mouth or anus to see these structures and assess any KS. Pacritinib is a capsule taken by mouth. Participants will take the drug twice a day, every day, for up to 24 weeks. They will write down each dose in a diary. Participants will visit the clinic 3 times in the first 4 weeks. Their visits will taper to once every 4 weeks. Imaging scans, blood tests, and other tests will be repeated during these visits. Participants will give samples of saliva. They may opt to allow tissues samples to be taken from their skin and lymph nodes. Participants will have follow-up visits 7 days and 30 days after their last dose of pacritinib. After that, they will visit the clinic every 3 months for up to 1 year. The physical exam and blood, heart, and imaging tests will be repeated at these visits.

* 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 (\3mg/L) * No life or organ-threatening manifestations of KSHV-MCD, KICS or Kaposi Sarcoma (KS) * Eastern Cooperative Oncology Group \[ECOG\] performance status \=60%) * Participants must have laboratory parameters as defined below: * Total bilirubin \