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

NCT01419561 | Recruiting Phase 2 FDA Drug

• 2 other identifiers: 11022011-C-0220
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

KSHV; HHV-8; KSHV Inflammatory Cytokine Syndrome (KICS)

Keywords

KSHV; KICS; HIV; Cytokines; HHV-8

Outcome Measures

Primary Outcomes (1)

• Natural history of KICS

  Description of the natural history of KICS, including the spectrum of clinical, laboratory and radiographic abnormalities seen in affected patients

  one year

Secondary Outcomes (1)

• Participants with KICS

  one year

Study Arms (6)

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)

Drug: Zidovudine; Drug: Valganiclovir

4

EXPERIMENTAL

Rituximab with or without liposomal doxorubicin (inactive)

Drug: Liposomal Doxorubicin; Drug: Rituximab

5

OTHER

Standard and alternative rational therapies (inactive)

Other: Standard Therapies

6

OTHER

Natural history

Other: Cohort 1

Interventions

Zidovudine DRUG

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.

3

Valganiclovir DRUG

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.

3

Rituximab DRUG

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.

4

Standard Therapies OTHER

Standard of Care drugs

5

Cohort 1 OTHER

Participants who are infected with KSHV who meet criteria for inflammatory cytokine syndrome (KICS)

6

Liposomal Doxorubicin DRUG

Liposomal doxorubicin (20 mg/m2) will be administered i.v. over 1 hour at day 1 of each cycle

4

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• \- 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.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (5)

• 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.

  PMID: 7997879 BACKGROUND

• Moore 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.

  PMID: 8523568 BACKGROUND

• Viejo-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.

  PMID: 15012001 BACKGROUND

• Ramaswami 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.

  PMID: 40763275 DERIVED

• Lage 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.

  PMID: 38941593 DERIVED

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

Zidovudine; liposomal doxorubicin; Rituximab

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Robert Yarchoan, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anaida Widell

CONTACT

(240) 760-6074; anaida.widell@nih.gov

Robert Yarchoan, M.D.

CONTACT

(240) 760-6075; robert.yarchoan@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2011
• First Posted: August 18, 2011
• Study Start: September 8, 2011
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: March 11, 2026

Record last verified: 2025-08-11

Locations

US (1)