KSHV Inflammatory Cytokine Syndrome (KICS) Clinical Trial
Official title:
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.
Background: - Pacritinib, is a JAK2/tyrosine kinase 3 inhibitor with negligible activity against JAK1 that also suppresses the interleukin-1 (IL-1) directed inflammatory pathway via inhibition of interleukin 1 receptor associated kinase. - Phase III studies of patients with myelofibrosis treated with pacritinib have demonstrated safety and efficacy as compared with best available treatment. - Pacritinib at 200mg twice daily emerged as the recommended dose in the treatment of myelofibrosis. - Through its activity on JAK2 and IRAK1, pacritinib blocks signaling through the interleukin 6 receptor (IL-6R); this should also include signaling through gp130 mediated by KSHV vIL-6. - In preliminary unpublished results, the Yarchoan lab has found that pacritinib is highly active against primary effusion lymphoma (PEL) cells in vitro. PEL is caused by Kaposi sarcoma-associated herpesvirus (KSHV), and most PEL affected patients are co-infected with Epstein-Barr virus (EBV). Like the plasmablasts of KSHV- multicentric Castleman disease (MCD), PEL cells are KSHV-infected B cells and thus can be a model for KSHV-MCD. - Given the overlapping cytokine profile between KSHV-MCD and KSHV-associated inflammatory cytokine syndrome (KICS) and elevated levels of IL6, we expect that pacritinib will have therapeutic effect in this disorder that is associated with excess inflammation. Objective: -To evaluate the clinical benefit of pacritinib in participants with symptomatic KSHV-MCD or KICS using a modified KSHV-MCD/KICS Clinical Benefit Response Criteria Eligibility: -Pathologically confirmed MCD or evidence of KICS Age >=18 - At least one clinical symptom and at least one laboratory attributable to KSHV-MCD or KICS - ECOG performance status <= 3 - No life- or organ-threatening manifestations of MCD or KICS - No concurrent diagnosis of PEL - No symptomatic pulmonary or visceral Kaposi Sarcoma (KS) Design: - Open label, single center pilot Phase II study. Eligible participants receive pacritinib orally 200mg twice daily until progression or up to 6 cycles. - Participants will be divided by prior therapy for KSHV-MCD (no prior therapy or prior therapy) and by diagnosis of KICS. - KICS and KSHV-MCD responses will be evaluated by KSHV-MCD Clinical Benefit Response Criteria every 4 weeks. - Interruptions to pacritinib will be permissible for treatment of worsening KS that develops on study and such interruptions may last up to 12 weeks. - Radiological assessment using PET-CT and CT will be used to assess response at 1, 3 and 6 months on study. - Total maximum number of evaluable participants to be enrolled is 54, with accrual ceiling set at 65 participants. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT01419561 -
Natural History Study of the KSHV Inflammatory Cytokine Syndrome (KICS)
|
Phase 2 |