Experimental Therapies for KICS

Recruiting at 1 trial location

Overseen By Robert Yarchoan, M.D.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Pregnancy, Grade 4 toxicity, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

140 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore treatments for KSHV inflammatory cytokine syndrome (KICS), a disease caused by a virus linked to cancer. The trial will test experimental therapies, including antiviral and chemotherapy drugs such as liposomal doxorubicin (a chemotherapy drug), rituximab (an immunotherapy drug), valganciclovir (an antiviral medication), and zidovudine (an antiretroviral drug), to find effective ways to manage the condition. Participants will undergo various tests, including medical history reviews, physical exams, and imaging studies, to gather information about how KICS affects the body. Individuals with the Kaposi sarcoma herpes virus and symptoms like fever, weight loss, or fluid buildup in the legs or abdomen might be a good fit for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in managing KICS.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It might depend on the specific treatments you receive during the study, so it's best to discuss this with the study researchers.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using rituximab with liposomal doxorubicin is generally safe and effective for treating conditions related to KSHV, such as Kaposi sarcoma. However, rituximab alone might worsen symptoms, so it should be combined with liposomal doxorubicin.

Studies have found that the combination of high-dose zidovudine and valganciclovir leads to significant health improvements, including reduced inflammation and a lower viral load. This suggests that the treatment is both effective and generally well-tolerated.

Both treatment combinations have been tested in studies and are considered safe overall. While side effects can occur, they are usually manageable. Prospective trial participants should discuss potential risks and benefits with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Kaposi's Sarcoma-associated Immune Reconstitution Inflammatory Syndrome (KICS) because they offer innovative approaches beyond the typical antiviral and chemotherapy regimens. Liposomal doxorubicin is unique because it uses a liposome delivery system, potentially reducing side effects and enhancing drug delivery to tumor sites. Rituximab targets CD20 on B-cells, which could help control the immune system's overreaction in KICS. Valganciclovir offers a targeted antiviral action against herpesviruses, which are thought to play a role in KICS, while zidovudine is known for its antiviral activity against HIV, addressing a potential underlying cause. These treatments could provide more comprehensive management of KICS by tackling the condition from different angles.

What evidence suggests that this trial's treatments could be effective for KICS?

Research has shown that rituximab combined with liposomal doxorubicin effectively treats conditions like KSHV-associated multicentric Castleman disease and Kaposi sarcoma. In this trial, one arm will explore rituximab with or without liposomal doxorubicin. This combination is chosen because rituximab alone can sometimes worsen Kaposi sarcoma, while adding liposomal doxorubicin helps control the disease more effectively. Another arm will investigate high doses of zidovudine and valganciclovir, which have improved health markers like C-reactive protein and albumin and reduced the KSHV virus in patients. These findings suggest that both treatment options could effectively manage KICS symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Robert Yarchoan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults with Kaposi sarcoma herpes virus and symptoms like fever, weight loss, or fluid accumulation. They must have evidence of the virus in blood or tissues and may also have related cancers. Participants need to use contraception and can't be pregnant. Those with severe unrelated health issues are excluded.

Inclusion Criteria

I am at risk for KSHV infection or have evidence of it.

I have at least two symptoms from different categories that might be due to KICS and can't be explained by other conditions.

I agree to use birth control during and after the study as required.

Exclusion Criteria

Biopsy proven KSHV-associated MCD

Pregnancy

I don't have severe health issues unrelated to HIV or KICS that would stop me from receiving the study treatments.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Natural History Observation

Participants are observed for the natural history of KSHV inflammatory cytokine syndrome (KICS) with regular study visits, medical history collection, physical exams, and sample collection.

1 year

Regular visits as determined by study researchers

Treatment (if required)

Participants with KICS requiring treatment may receive experimental treatments including antiviral and chemotherapy drugs.

Varies based on treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment or observation.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Liposomal Doxorubicin
• Rituximab
• Valganiclovir
• Zidovudine

Trial Overview The trial is studying how KSHV inflammatory cytokine syndrome (KICS) works and testing treatments including antiviral drugs like Valganiclovir and chemotherapy agents such as Rituximab, Zidovudine, Liposomal Doxorubicin against standard therapies.

How Is the Trial Designed?

Group I: 6 Experimental Treatment 1 Intervention

Natural history

Group II: 5 Experimental Treatment 1 Intervention

Standard and alternative rational therapies (inactive)

Group III: 4 Experimental Treatment 2 Interventions

Rituximab with or without liposomal doxorubicin (inactive)

Group IV: 3 Experimental Treatment 2 Interventions

High dose zidovudine + valganciclovir (inactive)

Group V: 2 Active Control 1 Intervention

Natural history/Observation arm (inactive)

Group VI: 1 Active Control 1 Intervention

Evaluation for Alternative Causes of KICS Symptoms (inactive)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Liposomal encapsulated doxorubicin (DOX-SL) was administered to 25 patients with HIV-related Kaposi's sarcoma, showing a defined response in 11 patients, with 9 achieving a partial response and 2 a complete response, indicating its efficacy as a treatment.

The treatment was well tolerated, with minimal acute toxicity and no reported cardiac toxicity, making DOX-SL a safe palliative option for patients with AIDS-related Kaposi's sarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of liposomal doxorubicin in the treatment of HIV-related Kaposi's sarcoma. Newell, M., Milliken, S., Goldstein, D., et al.[2019]

Caelyx/Doxil, a pegylated liposomal formulation of doxorubicin, has a unique pharmacokinetic profile that allows it to effectively target tumor sites while reducing toxicity compared to traditional doxorubicin.

It has been approved by the FDA and EMEA for treating AIDS-related Kaposi's sarcoma and recurrent epithelial ovarian cancer, and is being investigated for use in various other cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer. Tejada-Berges, T., Granai, CO., Gordinier, M., et al.[2022]

Liposomal doxorubicin was effective in treating Kaposi's sarcoma in HIV-infected patients, with five out of eight participants achieving a complete clinical response and three showing a partial response after six months of treatment.

While the treatment led to significant improvements, all patients experienced relapse after stopping therapy, highlighting the need for ongoing treatment; however, neutropenia was managed successfully with filgrastim, allowing for uninterrupted therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of Kaposi's sarcoma with liposomal doxorubicin. Bergin, C., O'Leary, A., McCreary, C., et al.[2019]

Liposomal formulations of doxorubicin (Doxil and Evacet) and daunorubicin (DaunoXome) have shown promise in clinical studies by reducing toxicity while maintaining or enhancing the effectiveness of these chemotherapy drugs.

Doxorubicin has already been approved for treating Kaposi's sarcoma and ovarian cancers, while daunorubicin is approved for Kaposi's sarcoma, with ongoing research likely to expand their clinical applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal encapsulated anthracyclines: new therapeutic horizons. Muggia, FM.[2022]

Pegylated liposomal doxorubicin (PLD) and daunorubicin citrate liposome (DNX) show higher response rates and less toxicity compared to conventional chemotherapy regimens for advanced Kaposi's sarcoma, making them more effective treatment options.

Patients treated with PLD or DNX experienced improved health-related quality of life in several areas, despite some common side effects like myelosuppression and stomatitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of liposomal anthracyclines in Kaposi's sarcoma. Krown, SE., Northfelt, DW., Osoba, D., et al.[2019]

In a phase II study involving 12 patients with refractory renal cell cancer, pegylated-liposomal doxorubicin (Doxil) was administered with mild toxicities, primarily related to mucositis and hand-foot syndrome.

Despite the treatment being well-tolerated, no objective responses were observed in 11 evaluable patients, indicating that pegylated-liposomal doxorubicin does not demonstrate efficacy in this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of pegylated-liposomal doxorubicin (Doxil) in renal cell cancer. Skubitz, KM.[2019]

In a Phase I/II study involving 15 patients with HIV-related cutaneous Kaposi's sarcoma, Doxil (liposomal doxorubicin) demonstrated a high partial response rate of 73%, indicating its efficacy as a palliative treatment for this severe condition.

Doxil was well tolerated among patients, with manageable toxicity primarily affecting blood cell counts, suggesting it is a safer option for patients with poor prognosis who have previously undergone chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi's sarcoma in AIDS. James, ND., Coker, RJ., Tomlinson, D., et al.[2019]

Stealth liposomal doxorubicin (Caelyx, Doxil) shows promise as a treatment for breast cancer, leveraging its unique liposomal formulation to improve drug delivery and efficacy.

The liposomal encapsulation of doxorubicin significantly alters its pharmacokinetics and reduces toxicity compared to traditional non-liposomal doxorubicin, making it a safer option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Caelyx (stealth liposomal doxorubicin) in the treatment of advanced breast cancer. Ranson, MR., Cheeseman, S., White, S., et al.[2019]

Liposomal anthracyclines, including pegylated and non-pegylated formulations of doxorubicin, have been developed to enhance the safety of traditional anthracyclines while maintaining their effectiveness against breast cancer.

These liposomal formulations are currently approved in Europe and Canada for treating metastatic breast cancer, aiming to reduce toxic side effects like cardiotoxicity, myelosuppression, and nausea.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of liposomal anthracyclines in breast cancer. Lorusso, V., Manzione, L., Silvestris, N.[2023]

Pegylated liposomal doxorubicin (Caelyx®/Doxil®) is an improved formulation of conventional doxorubicin that significantly reduces cardiotoxicity and enhances pharmacokinetics.

Clinical trials demonstrate that pegylated liposomal doxorubicin is effective in treating several cancers, including metastatic breast cancer and ovarian cancer, while maintaining a favorable safety profile compared to traditional chemotherapy agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin: a guide to its use in various malignancies. Lyseng-Williamson, KA., Duggan, ST., Keating, GM.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3143547/

High-dose zidovudine plus valganciclovir for Kaposi ... At the time of best response, the patients showed significant improvements in C-reactive protein, albumin, platelets, human IL-6, IL-10, and KSHV viral load.

2. academic.oup.com academic.oup.com/ofid/article/4/4/ofx196/4157744

Experience with Kaposi Sarcoma Herpesvirus Inflammatory ... In this series, we describe 2 cases that fulfill the working case definition of KICS and describe their clinical characteristics and outcomes.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01419561?term=peptide

Natural History Study of the KSHV Inflammatory Cytokine ... - KSHV inflammatory cytokine syndrome (KICS) is a newly recognized disease caused by Kaposi sarcoma-associated herpesvirus (KSHV). This virus can cause cancer.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11929155/

Modern Approach to Manage Patients With Kaposi Sarcoma Indeed, in MCD, prevention of viral reactivation by valganciclovir or zidovudine is an effective treatment [41]. On the opposite, valganciclovir ...

5. cureus.com cureus.com/articles/167158-a-challenging-case-of-kaposi-sarcoma-inflammatory-cytokine-syndrome

A Challenging Case of Kaposi Sarcoma Inflammatory ... A few treatments, such as rituximab plus liposomal doxorubicin and high-dose zidovudine plus valganciclovir, have shown some efficacy [5-7].

6. ashpublications.org ashpublications.org/bloodadvances/article-pdf/doi/10.1182/bloodadvances.2025016685/2405512/bloodadvances.2025016685.pdf

associated inflammatory cytokine syndrome (KICS) zidovudine plus valganciclovir for Kaposi sarcoma herpesvirus-associated multicentric. Castleman disease: a pilot study of virus-activated cytotoxic therapy ...