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
Intermittent or persistent fever for at least 1 week (>38 degrees C)
Fatigue (CTCAE - Grade >=2)
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
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.
Single group
Pacritinib
DrugPacritinib is administered orally as 200 mg twice daily for a total of 6, 28-day cycles
Clinical benefit
Percentage of participants with the best overall response of CR or PR to therapy.
Safety of pacritinib
Adverse events (AEs) will be reported by type and grade of toxicity
Time to treatment failure and duration of benefit
The interval between initiating therapy and the earliest of clinical progression and and the time from to disease progression or death in patients who achieve CR, PR, or SD.
Effect of pacritinib on concurrent diagnosis of Kaposi sarcoma (KS)
Fraction of participants who have a coexisting diagnosis of KS and who develop a response of any degree (PR; SD)
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