History of the KSHV Inflammatory Cytokine Syndrome (KICS)
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|ClinicalTrials.gov Identifier: NCT01419561|
Recruitment Status : Recruiting
First Posted : August 18, 2011
Last Update Posted : July 1, 2022
- 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.
- To collect genetic and medical information from people with KSHV inflammatory cytokine syndrome.
- Individuals at least 18 years of age who have Kaposi sarcoma herpes virus and symptoms that resemble those caused by KICS.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|KSHV Inflammatory Cytokine Syndrome (KICS) KSHV HHV-8||Drug: Zidovudine Drug: Liposomal Doxorubicin Drug: Valganiclovir Drug: Rituximab Other: Standard Therapies||Phase 2|
KSHV inflammatory cytokine syndrome (KICS) is a newly recognized syndrome caused by Kaposi sarcoma-associated herpesvirus (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.
The primary study objective is to enable intensive study and description of the natural history of KICS.
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
Patients with these characteristics will be further evaluated to identify those whose clinical and laboratory features are consistent with the working KICS working case definition to be followed in the natural history phase of the study.
This is a single center natural history cohort with a cohort of up to 80 patients. Of these, up to 40 who meet the criteria for KICS will then go onto a natural history arm, with two nested open label pilot treatment arms. Natural history patients will undergo clinical, laboratory and correlative assessment every 3 months until sustained resolution and two nested open label pilot treatment arms. Patients with clinical and laboratory manifestations of KICS, elevated inflammatory markers and KSHV viral load will be eligible for therapy with high dose zidovudine/valganciclovir, or if they have intercurrent Kaposi sarcoma (KS) requiring cytotoxic with rituximab/liposomal doxorubicin on the 2 nested open label pilot treatment arms. Each treatment arm uses a two-stage design, with interim analysis at 8 patients in each arm and potential accrual of 14 per arm. Patients on the treatment arm who have not responded to the pilot treatments or for whom such treatment would not be suitable may also be treated with best available therapy. Participants who require KS and/or primary effusion lymphoma (PEL) treatment following a KICS diagnosis will receive therapies within the appropriate arm of the study or be treated for their KS and/or PEL on a separate protocol while still followed on this study.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Natural History Study of the KSHV Inflammatory Cytokine Syndrome (KICS) Incorporating Pilot Evaluation of KSHV Targeted Therapies|
|Actual Study Start Date :||September 8, 2011|
|Estimated Primary Completion Date :||December 31, 2025|
|Estimated Study Completion Date :||December 31, 2025|
No Intervention: 1
Evaluation for Alternative Causes of KICS Symptoms
No Intervention: 2
Natural History/Observation Arm
High dose zidovudine + valganciclovir
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.
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.
Rituximab with or without liposomal doxorubicin
Drug: Liposomal Doxorubicin
Liposomal doxorubicin (20 mg/m2) will be administered i.v. over 1 hour at day 1 of each cycle
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 and alternative rational therapies
Other: Standard Therapies
Standard of Care drugs
- Natural history of KICS [ Time Frame: one year ]Description of the natural history of KICS, including the spectrum of clinical, laboratory and radiographic abnormalities seen in affected patients
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01419561
|Contact: Anaida Widell||(240) firstname.lastname@example.org|
|Contact: Robert Yarchoan, M.D.||(240) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office (888) NCI-1937|
|Principal Investigator:||Robert Yarchoan, M.D.||National Cancer Institute (NCI)|