Experimental Therapies for KICS

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Robert Yarchoan, M.D.

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: National Cancer Institute (NCI)

Disqualifiers: Pregnancy, Grade 4 toxicity, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the drug Liposomal Doxorubicin for treating KICS?

Liposomal Doxorubicin has been shown to be effective in treating Kaposi's sarcoma, particularly in patients with HIV, with studies reporting partial or complete resolution of symptoms. This suggests potential effectiveness for similar conditions like KICS, as both involve immune system complications.

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Is the treatment generally safe for humans?

Pegylated liposomal doxorubicin (Doxil, Caelyx) has been shown to have a favorable safety profile compared to conventional doxorubicin, with reduced heart-related side effects and mild skin and mouth-related toxicities. It has been used safely in various cancers, including breast and ovarian cancer, with ongoing studies to further understand its safety in combination treatments.

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How does the drug for KICS differ from other treatments?

The drug for KICS, which involves liposomal doxorubicin, is unique because it uses a special coating to help the medicine stay in the bloodstream longer and target tumor sites more effectively, reducing side effects compared to traditional chemotherapy. This approach has been shown to be effective in treating similar conditions like Kaposi's sarcoma with fewer side effects.

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Eligibility Criteria

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 18 years old or older.

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.

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.

Trial Timeline

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

Participant Groups

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.

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)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, MD

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

National Cancer Institute (NCI) Lead Sponsor

References

1. United States pubmed.ncbi.nlm.nih.gov

Liposomal encapsulated anthracyclines: new therapeutic horizons. [2022] After two decades of work in liposomal formulations for clinical use, two preparations containing doxorubicin (Doxil, ALZA, Pablo Alto, CA; and Evacet, The Liposome Company, Princeton, NJ), and one containing daunorubicin (DaunoXome; Gilead Sciences, Foster City, CA) have been undergoing widespread clinical study. Results have lived up to the promise that liposomal encapsulation may lead to toxicity attenuation, while retaining or even enhancing the efficacy of the parent anthracyclines. The eventual role of these agents in clinical practice is being defined in a number of studies that are reviewed herein. Already, approved indications have been achieved for doxorubicin against Kaposi's sarcoma and ovarian cancers, and for daunorubicin against Kaposi's sarcoma. The three compounds vary widely in their pharmacology, and these differences may contribute to their preferential localization into certain tumors. Additional indications for these liposomal encapsulated anthracyclines are likely to be established in the ensuing years.

2. England pubmed.ncbi.nlm.nih.gov

Treatment of Kaposi's sarcoma with liposomal doxorubicin. [2019] The efficacy of liposomal doxorubicin for treating Kaposi's sarcoma (KS) in patients infected with human immunodeficiency virus (HIV) was studied. Eight men with HIV infection and KS were to be given liposomal doxorubicin 20 mg/sq m i.v. monthly for six months and 10 mg/sq m i.v. monthly thereafter, depending on the response. They were assessed for the onset, extent, and duration of clinical response; relapse; adverse effects; development of new opportunistic infections; quality of life; and survival. Five patients had a clinical complete response (i.e., complete resolution of the manifestations of KS, as determined by physical examination but not confirmed by biopsy) and three patients had a partial response to the induction regimen of liposomal doxorubicin. Relapse occurred in all patients in whom therapy was stopped; reinstatement of therapy elicited a partial response. Neutropenia occurred in two patients; filgrastim therapy enabled the liposomal doxorubicin therapy to continue uninterrupted. Thromboembolic events developed or were suspected in three patients, although they may not have been caused by liposomal doxorubicin. Monthly i.v. administration of liposomal doxorubicin partially or completely eliminated the clinical manifestations of Kaposi's sarcoma in eight men infected with HIV.

3. Australia pubmed.ncbi.nlm.nih.gov

A phase II study of liposomal doxorubicin in the treatment of HIV-related Kaposi's sarcoma. [2019] To evaluate the toxicity and clinical efficacy of liposomal encapsulated doxorubicin (DOX-SL) in the treatment of HIV-related Kaposi's sarcoma (KS).

4. England pubmed.ncbi.nlm.nih.gov

Caelyx/Doxil for the treatment of metastatic ovarian and breast cancer. [2022] Caelyx/Doxil is a novel pegylated liposomal formulation of the first-generation anthracycline, doxorubicin. The pharmacokinetics of this polyethylene-glycol-coated liposome are characterized by a reduced volume of distribution, a long intravascular circulating half-life and slow plasma clearance compared with free doxorubicin. This, coupled with a small vesicular size, uniquely promotes the localization of Caelyx/Doxil at tumor sites and explains its altered toxicity profile. The FDA and EMEA have approved its use for the treatment of AIDS-related Kaposi's sarcoma and, more recently, for recurrent epithelial ovarian cancer (EOC). Numerous investigations have focused on its use in the treatment of metastatic breast cancer, as well as recurrent squamous cell cervical carcinoma, soft tissue sarcoma, squamous head and neck cancers, prostate cancers and malignant gliomas. Ongoing clinical studies of combination regimens incorporating Caelyx/Doxil will further clarify its role in the treatment of advanced solid tumors.

5. England pubmed.ncbi.nlm.nih.gov

Liposomal doxorubicin (Doxil): an effective new treatment for Kaposi's sarcoma in AIDS. [2019] The objective of this study was to assess the efficacy and toxicity of a novel Stealth liposomal encapsulated formulation of doxorubicin (Doxil). A Phase I/II dose escalation study was carried out in a specialist HIV oncology unit in a teaching hospital (predominantly in an outpatient department). Fifteen patients with HIV related, biopsy confirmed, cutaneous Kaposi's sarcoma, with or without visceral involvement of sufficient severity to require systemic chemotherapy, were treated. Most patients had poor prognosis disease as assessed by the Tumour/Immune status/Systemic symptoms (TIS) system and Karnofsky indices; six patients had previously received combination chemotherapy. Primary treatment consisted of a dose of Doxil 10 mg/m2, repeated after 2 weeks. If the Kaposi's sarcoma (KS) responded and the treatment was tolerated, the patient began maintenance therapy at the same dose every 2 weeks. If there was no clinical response, the dose was increased to 20 mg/m2 for the further two cycles, before proceeding to maintenance therapy. Treatment continued until other intercurrent disease, lack of further response, patient preference, or toxicity precluded further treatment. Tumour response was assessed 2 weeks after completion of at least two cycles of chemotherapy. Toxicity was assessed for each cycle. Doxil was well tolerated, and toxicity was manageable, the principal toxicity being haematological. A partial response rate of 11/15 (73%) was achieved, with disease stabilization in the remaining patients. We conclude that Doxil is an effective palliative treatment for epidemic KS in a patient group with a poor predicted outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

6. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of pegylated-liposomal doxorubicin (Doxil) in renal cell cancer. [2019] Twelve patients with refractory renal cell cancer were treated on a phase II study of pegylated-liposomal doxorubicin (Doxil). The initial dose per course was 55 mg/m2 every four weeks with dose modification based on mucositis and hand-foot syndrome (the main limiting toxicities). Toxicities were mild and similar to previous reports but dose reduction per the study protocol, which was designed to control the skin and mucosal toxicities, was common. No definite cardiac toxicity was observed. No objective responses were observed in 11 evaluable patients. This study did not demonstrate activity of pegylated-liposomal doxorubicin in renal cell cancer, although it can be given with mild toxicity.

7. New Zealand pubmed.ncbi.nlm.nih.gov

Pegylated liposomal doxorubicin: a guide to its use in various malignancies. [2018] Pegylated liposomal doxorubicin (Caelyx(®) [EU], Doxil(®) [USA]) represents an improved formulation of conventional doxorubicin, with reduced cardiotoxicity and an improved pharmacokinetic profile. As shown by evidence from clinical trials, intravenous pegylated liposomal doxorubicin is a useful option in the treatment of various malignancies, including metastatic breast cancer, ovarian cancer, multiple myeloma, and AIDS-related Kaposi sarcoma. It has a favourable safety profile relative to conventional doxorubicin and other available chemotherapy agents.

8. Netherlands pubmed.ncbi.nlm.nih.gov

Caelyx (stealth liposomal doxorubicin) in the treatment of advanced breast cancer. [2019] Anthracyclines are amongst the most active drugs in the treatment of breast cancer. Stealth liposomal doxorubicin (Caelyx, Doxil, Alza Pharmaceuticals Inc.) is a promising new agent under investigation for the treatment of breast cancer and other solid tumours. The liposomal encapsulation alters drug pharmacokinetics and leads to a marked change in toxicity profile compared to non-liposomal doxorubicin. The results of recently completed and ongoing clinical trials in breast cancer are reviewed.

9. England pubmed.ncbi.nlm.nih.gov

Role of liposomal anthracyclines in breast cancer. [2023] Anthracyclines are among the most effective drugs for patients with breast cancer. Their use, however, has been limited by associated toxic effects, including myelosuppression, alopecia, nausea and vomiting, stomatitis, and most importantly, cardiotoxicity. Liposomal anthracyclines were developed to increase the therapeutic index of conventional anthracyclines by maintaining antitumor efficacy while improving the safety profile. There are currently two liposomal formulations available for treatment of advanced disease: a not pegylated liposomal doxorubicin and a pegylated liposomal doxorubicin. This review will focus on both liposomal formulations of doxorubicin which are approved in Europe and Canada for use in patients with metastatic breast cancer.

10. United States pubmed.ncbi.nlm.nih.gov

Use of liposomal anthracyclines in Kaposi's sarcoma. [2019] Conventional chemotherapy regimens for the treatment of advanced Kaposi's sarcoma (KS) show limited efficacy and considerable toxicity. Liposomal anthracyclines with potential utility in KS include pegylated liposomal doxorubicin (Doxil/Caelyx [PLD]), daunorubicin citrate liposome (DaunoXome [DNX]), and nonpegylated liposomal doxorubicin (Myocet [NPLD]). Preclinical data showed that pegylated liposomes accumulate preferentially in highly vascularized KS lesions. In randomized clinical trials, PLD induced higher response rates than did the conventional combination chemotherapy regimens, bleomycin + vincristine (BV) and BV + conventional doxorubicin (ABV); DNX produced a response rate comparable to that of ABV. NPLD has not been compared with conventional chemotherapy for KS. PLD and DNX were associated with less toxicity compared with BV or ABV, including less alopecia and fewer gastrointestinal and neurologic side effects. Grade 3/4 myelosuppression was common with both PLD and DNX; stomatitis and infusion reactions occurred with PLD treatment, but hand-foot syndrome was relatively infrequent in the dose schedules used for KS. Health-related quality of life was improved in several domains in patients treated with PLD or DNX compared with ABV.