Clinical Trial: Virotherapy and Natural History Study of KHSV-Associated Multricentric Castleman s Disease With Correlates of Disease Activity

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Targeted Oncolytic Virotherapy and Natural History Study of KSHV-Associated Multicentric Castleman's Disease With Laboratory and Clinical Correlates of Disease Activity

Brief Summary:

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.

Patients ages 12 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 patients 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 gastro

Detailed Summary:

Background:

  • 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 patients and also provide a model for further development of this approach in other tumors.

Objectives

  • To study and describe the natural history of KSHV-MCD.
  • To assess disease activity as reflected by fever, thrombocytopenia, anemia, neutropenia, and lymphocytopenia, human and viral interleukin-6 levels, C-reactive protein, and KSHV viral loads.
  • To describe how the laboratory pathogenesis-related parameters (especially serum levels of human and viral interleukin-6) are related to the clinica
    Sponsor: National Cancer Institute (NCI)

    Current Primary Outcome: Describe natural history [ Time Frame: Study Closure ]

    Original Primary Outcome:

    Current Secondary Outcome: Therapeutic efficacy and toxicity of several rationally designed therapeutic approaches to KSHV-MCD [ Time Frame: 21 days ]

    Original Secondary Outcome:

    Information By: National Institutes of Health Clinical Center (CC)

    Dates:
    Date Received: September 21, 2004
    Date Started: September 17, 2004
    Date Completion: October 1, 2020
    Last Updated: May 12, 2017
    Last Verified: October 6, 2016