Virotherapy for Castleman Disease
Trial Summary
What is the purpose of this trial?
This study will gain information about a rare disorder called KSHV-associated multicentric Castleman s disease (MCD). KSHV, a virus, causes several kinds of cancer, including some forms of MCD. KSHV stands for the Kaposi s sarcoma herpes virus, also called human herpes virus-8, or HHV-8. Researchers want to understand the biology of KSHV-MCD to identify how this disease causes illness and to find ways to treat it. There is no standard therapy effective for all cases of KSHV-MCD. The disease is often fatal, and about half the people who have it die within 2 years of diagnosis. Participants ages 18 and older may be eligible for this study. Participation entails more drawing of blood and having repeated tumor biopsies than if patients received treatment in a non-research setting. Researchers would like to learn more about the relationship of KSHV and Castleman s disease symptoms, and they want to obtain at least three biopsies in this study. There are some side effects of experimental therapy that participants may take for KSHV-MCD. Zidovudine, or Retrovir , is used at a high dose. It is given orally or through a vein, four times daily, for 7 days or longer. Zidovudine can cause nausea, vomiting, decreased bone marrow function, and decreased blood counts. Combined with valganciclovir, or Valcyte , it is likely to be more toxic to bone marrow. Valganciclovir can cause problems with bone marrow function, leading to low blood counts, sterility, and defects in a fetus. Combined with zidovudine, valganciclovir may cause more toxicity to the bone marrow. It is given twice daily for 7 days or longer. Bortezomib, or Velcade , is given for a few seconds by a rapid push through a needle into the vein. It is given twice weekly for four doses and then stopped for 1 week. Bortezomib can sometimes cause low blood pressure; it also can cause gastrointestinal problems and a low blood platelet count. Rituximab and liposomal doxorubicin are drugs given by a catheter into a vein. Interferon-alpha is given by injection into the skin. Those drugs are not experimental, but their use in Castleman s disease is experimental. Some participants may be treated with a combination of chemotherapy followed by interferon-alpha. Interferon-alpha is infected into the skin by a needle. The natural form of interferon is produced by the body and helps to control viral infections. KSHV decreases the effect of the body s interferon, and the researchers want to see if giving higher doses of interferon will help to control KSHV infection. A positron emission tomography (PET) scan, for research purposes only, may be done up to three times a year. A radioactive sugar molecule called fluorodeoxyglucose, or FDG, is used. It is believed that activated lymphocytes that may be found in participants disease might use more FDG because these cells burn more glucose fuel. This study may or may not have a direct benefit for participants. However, detailed assessments made throughout the study may provide information to help the doctors treat KSHV-MCD better.
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.
What data supports the effectiveness of the drug for Castleman Disease?
The research indicates that rituximab, an anti-CD20 therapy, and anti-interleukin-6 therapies have shown effectiveness in treating multicentric Castleman's disease, particularly in cases associated with human herpes virus 8. These therapies target specific factors involved in the disease, improving outcomes for patients.12345
How does virotherapy differ from other treatments for Castleman disease?
Virotherapy is unique because it uses viruses to target and destroy disease cells, which is different from traditional treatments like surgery, radiation, or chemotherapy that focus on removing or killing cells through physical or chemical means. This approach may offer a novel way to treat Castleman disease, especially when standard treatments are not effective or applicable.26789
Research Team
Robert Yarchoan, M.D.
Principal Investigator
National Cancer Institute (NCI)
Eligibility Criteria
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
Exclusion Criteria
Timeline
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive various treatments including high-dose zidovudine, valganciclovir, bortezomib, sirolimus, rituximab with liposomal doxorubicin, and EPOCH chemotherapy
Follow-up
Participants are monitored for safety and effectiveness after treatment
Natural History Observation
Participants are observed to study and describe the natural history of KSHV-MCD
Treatment Details
Interventions
- Bortezomib
- Cyclophosphamide
- Doxorubicin
- Etoposide
- Interferon-alpha
- Liposomal Doxorubicin
- Prednisone
- Rituximab
- Valganciclovir
- Virotherapy
- Zidovudine
Find a Clinic Near You
Who Is Running the Clinical Trial?
National Cancer Institute (NCI)
Lead Sponsor