Understanding KSHV Inflammatory Cytokine Syndrome

Natural History Study of the KSHV Inflammatory Cytokine Syndrome (KICS)

This study is trying to learn more about KSHV inflammatory cytokine syndrome by gathering health information from people diagnosed with it to understand how the condition develops and changes over time.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 140 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (nih)
• Drugs / interventions: chemotherapy
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT01419561 on ClinicalTrials.gov

What this trial studies

This study aims to gather genetic and medical information from individuals diagnosed with KSHV inflammatory cytokine syndrome (KICS), a condition caused by the Kaposi sarcoma-associated herpesvirus (KSHV). Participants will undergo regular study visits where they will provide a complete medical history and undergo physical examinations. The study focuses on assessing the natural history of KICS, including the clinical, laboratory, and radiographic abnormalities associated with the syndrome. By collecting this data, researchers hope to better understand the disease and its progression.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 18 and older who exhibit symptoms potentially attributable to KICS and have evidence of KSHV infection.

Not a fit: Patients without symptoms related to KICS or those with KSHV-associated multicentric Castleman disease may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved understanding and treatment options for patients suffering from KICS.

How similar studies have performed: While KICS is a newly recognized syndrome, similar studies on KSHV and its associated conditions have shown promise in understanding the disease mechanisms.

Eligibility criteria

* INCLUSION CRITERIA:
* Age greater than or equal to18 Years.
* Any HIV status.
* At least two manifestations drawn from at least two of the categories (clinical symptoms, laboratory abnormalities and/or radiographic abnormalities), which are at least possibly attributable to KICS and are not readily explicable from known medical conditions in the participant:
* Clinical symptoms (each at least grade 1 by CTCAE definitions)
* Fever (\>38 degrees C), chills or rigors
* Fatigue or lethargy
* Cachexia or edema
* Cough, dyspnea, airway hyperreactivity, or nasal inflammation
* Nausea, anorexia, abdominal pain or altered bowel habit
* Athralgia or myalgia
* Altered mental state
* Neuropathy with or without pain
* Laboratory abnormalities
* Anemia (hemoglobin\<12.0g/dL)
* Thrombocytopenia (platelets\<100,000 cells/microL)
* Leukopenia (white cell count\<4,000 cells/microL)
* Hypoalbuminemia (albumin\<3.5g/dL)
* Hyponatremia (sodium\<135mmol/L)
* Coagulopathy (PT or PTT \>1.5 times upper limit of normal)
* Radiographic Abnormalities
* Pathologic lymphadenopathy (at least five discrete nodes each \>1cm in their longest dimension)
* Splenomegaly (\>12 cm in the longest dimension)
* Hepatomegaly (\>17cm in the longest dimension)
* Body cavity effusions not caused by primary effusion lymphoma nor chylous effusions directly related to lymphatic infiltration by KS
* C-reactive protein (CRP) \>3mg/L.
* Exposure risk for KSHV infection (including being a first or second generation immigrant from an endemic area, or male-to-male sexual activity) or evidence of KSHV infection demonstrated by one of:

  * Molecular evidence of KSHV in whole blood, or KSHV VL levels within circulating PBMCs as determined by the Whitby laboratory
  * Immunohistochemical evidence of KSHV in tissues (for example by staining for LANA or vIL-6) confirmed in the Laboratory of Pathology (LP), CCR, NCI.
  * Presence of KS or PEL (KSHV-associated malignancies), confirmed in the LP, CCR, NCI.
* Women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of study participation, and after treatment (if received), according to drug requirements. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

EXCLUSION CRITERIA:

\- Biopsy proven KSHV-associated MCD, confirmed in the LP, CCR, NCI.

Note: In collaboration with LP, we have recently found that some participants with KICS but without a lymph node or splenic diagnosis of MCD have MCD-like cells in their effusions or circulating blood. This may in fact represent a newly recognized form of KSHV-MCD, but our analysis continues. While certain of these participants were historically included in this study, given this new understanding, they will not be entered on this protocol and removed if liquid MCD is diagnosed.

* Pregnancy
* Any abnormality that would be scored as NCI CTC Grade 4 toxicity that is unrelated to HIV, its treatment, or to KICS that would preclude the use of all of the study treatments or the ability to monitor the natural history of KICS untreated.
* Any condition or set of circumstances that in the opinion of the investigators would make participation in this study unsafe or otherwise inappropriate for a given individual.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (RECRUITING)

Study contacts

• Principal investigator: Robert Yarchoan, M.D. — National Cancer Institute (NCI)
• Study coordinator: Anaida Widell

Conditions: KSHV Inflammatory Cytokine Syndrome, KSHV, HHV-8, KICS, HIV, Cytokines