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


N/A
12 Years
N/A
Open (Enrolling)
Both
Giant Lymph Node Hyperplasia

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Trial Information

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


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 clinical and hematologic
parameters listed.

Eligibility

- Age greater than or equal to 12 years

- Biopsy proven KSHV-associated MCD

Design

- 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

- Sirolimus

- Rituximab with liposomal doxorubicin followed by interferon-alpha

- Rituximab with EPOCH chemotherapy

Inclusion Criteria


- INCLUSION CRITERIA:

Age greater than or equal to 12 years.

Biopsy proven KSHV-associated MCD, confirmed in the Laboratory of Pathology, CCR.

Willing to give informed consent.

-A parent or guardian must be available for giving consent for pediatric subjects under 18
years of age.

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.

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.

Type of Study:

Observational

Study Design:

N/A

Principal Investigator

Robert Yarchoan, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

040275

NCT ID:

NCT00092222

Start Date:

September 2004

Completion Date:

Related Keywords:

  • Giant Lymph Node Hyperplasia
  • HHV-8
  • HIV
  • Malignancy
  • Lymphoproliferation
  • Lymph Node Hyperplasia
  • Multicentric Castleman DIsease
  • MCD
  • KSHV-MCD
  • KSHV Associated MCD
  • HIV Infections
  • Herpes Viruses
  • Giant Lymph Node Hyperplasia
  • Hyperplasia

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892