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.
• 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.