KSHV Inflammatory Cytokine Syndrome (KICS)Phase 2NCT01419561
Natural History Study of the KSHV Inflammatory Cytokine Syndrome (KICS)
A Phase 2 study testing Zidovudine, Liposomal Doxorubicin and Valganiclovir in people with KSHV Inflammatory Cytokine Syndrome (KICS) and KSHV, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- KSHV Inflammatory Cytokine Syndrome (KICS), KSHV, HHV-8
- What is being tested?
- Zidovudine, Liposomal Doxorubicin and Valganiclovir
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 140 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Sep 2011to 31 Dec 2028
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
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.
Read more
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....
Read the detailed description
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
- Adults of any HIV status with:
- At least two symptoms, laboratory or radiographic abnormalities which are at least possibly attributable to KICS (including fever, fatigue, cachexia, edema, respiratory or gastrointestinal symptoms, hematologic cytopenias, hypoalbuminemia, hyponatremia, lymphadenopathy, organomegaly, effusions)
- C-reactive protein >3mg/L
- Evidence of KSHV infection or a risk exposure for KSHV infection
- No evidence of KSHV-associated multicentric Castleman disease
- Participants with these characteristics will be further evaluated to identify those whose clinical and laboratory features are consistent with the KICS working case definition to be followed in the natural history phase of the study.
Design
-This is a single center natural history study with a cohort of up to 120 evaluable participants. Participants who meet the criteria for KICS will go onto a natural history arm, which permits observation for KICS with or without other concurrent KSHV-associated disorders. Participants who require KS and/or primary effusion lymphoma (PEL) treatment along with a KICS diagnosis will receive rational therapies for these conditions or be treated for their KS and/or PEL on a separate protocol while still followed on this study.
- Conditions
- KSHV Inflammatory Cytokine Syndrome (KICS), KSHV, HHV-8
- Being tested
- Zidovudine, Liposomal Doxorubicin, Valganiclovir, Rituximab, Standard Therapies
- Keywords
- KSHV, KICS, HIV, Cytokines, HHV-8
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ZidovudineDrug
Zidovudine 600 mg will be administered orally 4 times a day or i.v. at 300 mg every 6 hours for 14 days for cycle 1 and for 7 days (up to additional 7 days if ongoing symptoms) for following cycles.
Liposomal DoxorubicinDrug
Liposomal doxorubicin (20 mg/m2) will be administered i.v. over 1 hour at day 1 of each cycle
ValganiclovirDrug
Valganciclovir (900mg) will be administered orally twice/day or Ganciclovir (5 mg/kg) will be administered i.v. over 1 hour for 14 days for cycle 1 and for 7 days (up to additional 7 days if ongoing symptoms) for following cycles.
RituximabDrug
Rituximab (375 mg/m2) will be admnistered i.v. at 50 mg/hr up to 100 mg/hr at day 1 of the first cycle and at 100mg/hr up to 400 mg
/hr at day 1 of following cycles.
Standard TherapiesOther
Standard of Care drugs
Cohort 1Other
Participants who are infected with KSHV who meet criteria for inflammatory cytokine syndrome (KICS)
| Study group | Role | What they receive |
|---|---|---|
| 1 | No intervention | Evaluation for Alternative Causes of KICS Symptoms (inactive) |
| 2 | No intervention | Natural history/Observation arm (inactive) |
| 3 | Experimental | High dose zidovudine + valganciclovir (inactive) Receives: Drug: Zidovudine; Drug: Valganiclovir |
| 4 | Experimental | Rituximab with or without liposomal doxorubicin (inactive) Receives: Drug: Liposomal Doxorubicin; Drug: Rituximab |
| 5 | Other | Standard and alternative rational therapies (inactive) Receives: Other: Standard Therapies |
| 6 | Other | Natural history Receives: Other: Cohort 1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Natural history of KICS
Description of the natural history of KICS, including the spectrum of clinical, laboratory and radiographic abnormalities seen in affected patients
Measured: one year
Secondary outcomes (1)
Participants with KICS
Evaluate the survival of participants with KICS and of KICS with primary effusion lymphoma (PEL)
Measured: one year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Aug 2011 (estimated)
- Study start8 Sep 2011
- Primary completion31 Dec 2028 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for KSHV Inflammatory Cytokine Syndrome (KICS)Studies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Robert Yarchoan, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01419561
- Sponsor's protocol ID
- 110220
- Other IDs
- 11-C-0220
- Status last verified
- 13 Oct 2026
- First submitted
- 17 Aug 2011
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J, Knowles DM, Moore PS. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865-9. doi: 10.1126/science.7997879.
PubMed 7997879Moore PS, Gao SJ, Dominguez G, Cesarman E, Lungu O, Knowles DM, Garber R, Pellett PE, McGeoch DJ, Chang Y. Primary characterization of a herpesvirus agent associated with Kaposi's sarcomae. J Virol. 1996 Jan;70(1):549-58. doi: 10.1128/JVI.70.1.549-558.1996.
PubMed 8523568Viejo-Borbolla A, Schulz TF. Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8): key aspects of epidemiology and pathogenesis. AIDS Rev. 2003 Oct-Dec;5(4):222-9.
PubMed 15012001Ramaswami R, Lurain K, Polizzotto MN, Widell A, Ekwede I, Tassi E, Rupert A, Marshall VA, Roth MJ, Filie AC, Pittaluga S, Jaffe ES, Wang HW, Whitby D, Uldrick TS, Yarchoan R. Characteristics and outcomes of Kaposi sarcoma herpesvirus-associated inflammatory cytokine syndrome. Blood Adv. 2025 Nov 25;9(22):5720-5731. doi: 10.1182/bloodadvances.2025016685.
PubMed 40763275Lage SL, Ramaswami R, Rocco JM, Rupert A, Davis DA, Lurain K, Manion M, Whitby D, Yarchoan R, Sereti I. Inflammasome activation in patients with Kaposi sarcoma herpesvirus-associated diseases. Blood. 2024 Oct 3;144(14):1496-1507. doi: 10.1182/blood.2024024144.
PubMed 38941593