Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity
- - INCLUSION CRITERIA: Age greater than or equal to 18 years. Biopsy proven KSHV-associated MCD, confirmed in the Laboratory of Pathology, CCR. Willing to give informed consent. EXCLUSION CRITERIA: Any abnormality that would be scored as NCI CTC Grade IV toxicity that is unrelated to HIV, its treatment, or to MCD that would preclude protocol treatment and/or observation only. Presence of another malignancy requiring current treatment that would preclude the use of all of the study treatments or the ability to monitor the natural history of MCD untreated. Pregnant women are excluded from this study as certain of the study agents have the potential for teratogenic effects Any condition or set of circumstances that in the opinion of the investigators would make participation in this study unsafe or otherwise inappropriate for a given individual.
- Multicentric Castleman's disease (MCD) is a rare but lethal Kaposi's sarcoma-associated
herpesvirus (KSHV) associated lymphoproliferative disorder with a median survival of 2
years. It occurs more often in HIV-infected individuals than those without HIV
infection. The poor prognosis is not fully explained by the underlying HIV, as the
HIV-negative cases appear to have no survival advantage over the HIV-positive cohort.
The disease has no defined standard treatment and has not been prospectively studied in
a comprehensive manner.
- KSHV-MCD may provide a model for the development of targeted oncolytic virotherapy or
other pathogenesis-based approaches to viral-associated malignancies. In KSHV-MCD, viral
encoded tyrosine kinase genes appear to be possible targets to exploit in a virotherapy
approach. Specific viral encoded genes appear to convert zidovudine and ganciclovir (or
valganciclovir) into toxic phosphorylated moieties within the KSHV-infected tumor cells,
to specifically target the KSHV-infected cells thus leading to specific cell death. If
successful, this could have direct therapeutic benefit to participants and also provide
a model for further development of this approach in other tumors.
-To study and describe the natural history of KSHV-MCD.
- Age greater than or equal to 18 years
- Biopsy proven KSHV-associated MCD
- Natural History study
- Inclusion of treatment as needed, with guidelines for preliminary investigation of a
variety of specific treatments of interest
- High-dose zidovudine and ganciclovir
- High-dose zidovudine and ganciclovir and bortezomib
- Rituximab with liposomal doxorubicin followed by interferon-alpha
- Rituximab with EPOCH chemotherapy
Trial Phase Phase II
Trial Type Treatment
National Cancer Institute
- Primary ID 040275
- Secondary IDs NCI-2019-00301, 04-C-0275, NCI-2013-02049
- Clinicaltrials.gov ID NCT00092222