Natural History Study of the KSHV Inflammatory Cytokine Syndrome (KICS)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Natural history of KICS
研究概览
简要总结
Background:
- KSHV inflammatory cytokine syndrome (KICS) is a newly recognized disease caused by Kaposi sarcoma-associated herpesvirus (KSHV). This virus can cause cancer. People with KICS can have severe symptoms. They include fever, weight loss, and fluid in the legs or abdomen. People with KICS may also be at risk of getting other cancers associated with KSHV. These cancers include Kaposi sarcoma and lymphoma. Because KICS is a newly identified disease, more information is needed on how the disease works and what can be done to treat it.
Objectives:
- To collect genetic and medical information from people with KSHV inflammatory cytokine syndrome.
Eligibility:
- Individuals at least 18 years of age who have Kaposi sarcoma herpes virus and symptoms that resemble those caused by KICS.
Design:
- Participants will have regular study visits. The schedule will be determined by the study researchers.
- Participants will provide a complete medical history and have a full physical exam. Blood and urine samples will be collected as well.
- People with KICS that requires treatment may get new experimental treatments. These treatments may include antiviral drugs and chemotherapy drugs, depending on the nature of the disease.
- Participants will have imaging studies, such as chest x-rays and computed tomography scans, to study the tumors.
- Bone marrow and lymph node biopsies may be done to collect tissue samples for study.
- Participants who have Kaposi sarcoma will have photographs taken of their lesions....
详细描述
Background
-Kaposi sarcoma-associated herpesvirus (KSHV) inflammatory cytokine syndrome (KICS) is a newly recognized syndrome caused by KSHV. It is characterized by severe inflammatory symptoms including fevers, wasting, cytopenias, hypoalbuminemia, and hyponatremia, associated in some cases with lymphadenopathy or effusions, without pathological evidence of MCD. Patients with KICS exhibit elevated KSHV viral loads and cytokine dysregulation, with elevations of IL-6, IL-10, and a KSHV-encoded IL-6 homolog, viral IL-6.
Objective
-Assessment of the natural history of KSHV inflammatory cytokine syndrome (KICS), including the spectrum of clinical, laboratory and radiographic abnormalities seen in affected participants.
Eligibility
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •- 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.
研究组 & 干预措施
5
Standard and alternative rational therapies (inactive)
干预措施: Standard Therapies (Other)
3
High dose zidovudine + valganciclovir (inactive)
干预措施: Zidovudine (Drug)
6
Natural history
干预措施: Cohort 1 (Other)
1
Evaluation for Alternative Causes of KICS Symptoms (inactive)
3
High dose zidovudine + valganciclovir (inactive)
干预措施: Valganiclovir (Drug)
2
Natural history/Observation arm (inactive)
4
Rituximab with or without liposomal doxorubicin (inactive)
干预措施: Liposomal Doxorubicin (Drug)
4
Rituximab with or without liposomal doxorubicin (inactive)
干预措施: Rituximab (Drug)
结局指标
主要结局
Natural history of KICS
时间窗: one year
Description of the natural history of KICS, including the spectrum of clinical, laboratory and radiographic abnormalities seen in affected patients
次要结局
- Participants with KICS(one year)