Virotherapy for Castleman Disease

Not currently recruiting at 1 trial location
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RY
Overseen ByRobert Yarchoan, M.D.
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: National Cancer Institute (NCI)
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatments for KSHV-associated multicentric Castleman's disease (MCD), a rare and potentially life-threatening condition linked to a virus. The study tests various treatments, including drugs like zidovudine, which can affect blood cells, and valganciclovir, which may impact bone marrow, to determine their effectiveness in managing the disease. Additionally, the trial includes virotherapy, a treatment that uses viruses to target and destroy cancer cells. Individuals diagnosed with KSHV-MCD who are willing to undergo blood draws and tumor biopsies might be suitable candidates. The trial aims to enhance understanding of the disease and improve future treatments, though direct benefits to participants are not guaranteed. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, since the study involves experimental treatments, it's best to discuss your current medications with the study team to ensure safety and compatibility.

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

Research has shown that various treatments for KSHV-associated multicentric Castleman disease (MCD) have been tested for safety in people. High doses of zidovudine and valganciclovir can cause side effects such as nausea, vomiting, and bone marrow issues, leading to lower blood counts. This combination may be more harmful to the bone marrow when used together.

Bortezomib, combined with zidovudine and valganciclovir, might cause low blood pressure and stomach problems. Previous studies found that rituximab with liposomal doxorubicin is generally safe for most patients, with mild to moderate side effects like infections. This combination has effectively treated symptoms of KSHV-MCD.

Sirolimus has also shown promise in other studies. It has been tested for long-term safety and is being considered as a new treatment option for related conditions.

In summary, while these treatments can have side effects, studies have provided important safety information. Participants should weigh both the potential benefits and risks of joining the trial.12345

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for Castleman Disease, which often involve chemotherapy and immunotherapy, virotherapy offers a novel approach by harnessing viruses to target and destroy abnormal cells. Researchers are excited about virotherapy because it specifically targets diseased cells without affecting healthy ones, potentially reducing side effects commonly associated with traditional treatments. Additionally, virotherapy could enhance the immune system's ability to fight the disease, providing a two-pronged attack that is both direct and supportive. This innovative mechanism of action sets virotherapy apart from the usual treatment options and holds promise for more effective and gentler management of Castleman Disease.

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

Research has shown that there isn't a one-size-fits-all treatment for KSHV-associated multicentric Castleman's disease (KSHV-MCD), a serious condition often linked to Kaposi's sarcoma herpesvirus (KSHV). In this trial, one group receives high doses of zidovudine and valganciclovir, which typically delayed disease progression for 6 months, with 86% of patients surviving after a year. Another group uses sirolimus, effective for similar conditions and generally well-tolerated. A separate group combines EPOCH chemotherapy with rituximab, benefiting 77% of patients, with more than half achieving complete remission. Additionally, another group studies rituximab with liposomal doxorubicin, showing significant improvement in patients with extensive prior treatments. These treatments are under study for their potential to manage KSHV-MCD, but results can vary among individuals.678910

Who Is on the Research Team?

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Robert Yarchoan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults over 18 with biopsy-proven KSHV-associated multicentric Castleman's disease can join this study. Pregnant women and individuals with severe unrelated health issues, other active malignancies needing treatment, or conditions making the trial unsafe are excluded.

Inclusion Criteria

My condition is confirmed as KSHV-associated MCD by a pathology lab.
Willing to give informed consent

Exclusion Criteria

I do not have another cancer that needs treatment interfering with this study.
I don't have severe health issues unrelated to HIV or my current condition that would stop me from following the study's treatment plan.
Pregnant women are excluded from this study as certain of the study agents have the potential for teratogenic effects
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Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various treatments including high-dose zidovudine, valganciclovir, bortezomib, sirolimus, rituximab with liposomal doxorubicin, and EPOCH chemotherapy

Varies based on treatment response

Follow-up

Participants are monitored for safety and effectiveness after treatment

Until study closure

Natural History Observation

Participants are observed to study and describe the natural history of KSHV-MCD

Ongoing

What Are the Treatments Tested in This Trial?

Interventions

  • Bortezomib
  • Cyclophosphamide
  • Doxorubicin
  • Etoposide
  • Interferon-alpha
  • Liposomal Doxorubicin
  • Prednisone
  • Rituximab
  • Valganciclovir
  • Virotherapy
  • Zidovudine
Trial Overview The trial is exploring treatments for a rare cancer-like condition caused by KSHV virus. It includes drugs like Zidovudine and Valganciclovir (which may affect bone marrow), Bortezomib (possible low blood pressure), Rituximab, Doxorubicin, Interferon-alpha (to boost immune response against the virus), and others.
How Is the Trial Designed?
6Treatment groups
Active Control
Group I: Active Treament 3Active Control3 Interventions
Group II: Active Treatment 1Active Control1 Intervention
Group III: Active Treatment 2Active Control7 Interventions
Group IV: Active Treatment 4Active Control3 Interventions
Group V: Active Treatment 5Active Control2 Interventions
Group VI: Natural HistoryActive Control1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials
14,080
Recruited
41,180,000+

Citations

1.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/39368885/
Real World Data on Efficacy and Safety of EPOCH in T-Cell ...In 36 evaluable patients, the overall response rate (ORR) was 77% (95% CI, 61%-89%) with 19 (53%) patients achieving complete response (CR) (95% CI, 36%-69%).
2.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/10506727/
Chemotherapy with etoposide, vincristine, doxorubicin ...Results: After a median of 5 cycles (range, 1-9 cycles), 4 patients achieved a complete response (27%) and 8 patients achieved a partial response (53%) for an ...
783-DA-R-EPOCH (dose adjusted rituximab etoposide ...This study was designed to assess the efficacy and safety of an infusional DA-EPOCH (dose-adjusted etoposide/vincristine/doxorubicin/bolus cyclophosphamide/ ...
NCT03023046 | Etoposide, Prednisone, Vincristine Sulfate ...This phase II trial studies how well etoposide, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin (DA-EPOCH) works in treating patients ...
R-DA-EPOCH is 'Highly Effective Therapy' for PMBLThe three-year progression-free survival was 92.8% (95% CI, 88.1-97.7), and three-year overall survival was 97.2% (95% CI, 94.2-100). There were ...
High-dose zidovudine plus valganciclovir for Kaposi ...In a pilot study, 14 HIV-infected patients with symptomatic KSHV-MCD received high-dose zidovudine (600 mg orally every 6 hours) and the oral prodrug, ...
Virotherapy and Natural History Study of KHSV-Associated ...This study will gain information about a rare disorder called KSHV-associated multicentric Castleman s disease (MCD). KSHV, a virus, causes several kinds of ...
Successful treatment with bortezomib in combination ...Bortezomib combined with dexamethasone may be an effective salvage strategy for severe and refractory iMCD.
This label may not be the latest approved by FDA. For current ...The safety data described below and in Table 10 reflect exposure to either VELCADE (n=331) or dexamethasone (n=332) in a study of patients with relapsed ...
Castleman DiseaseCastleman Disease ; Anakinra · CD19 ; Bortezomib/DexAMETHasone · CD17 ; Bortezomib/DexAMETHasone + RiTUXimab · CD18 ; CHOP (CycloPHOSphamide/DOXOrubicin/VinCRIStine/ ...
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