Antiretroviral Therapy With or Without Bortezomib or Combination Chemotherapy and Rituximab or Sirolimus Only or Observation Only in Treating Patients With Castleman's Disease

OBJECTIVES:

Primary

- Determine disease activity, as reflected by fever, thrombocytopenia, anemia,
neutropenia, and lymphocytopenia; human and viral interleukin-6 levels; C-reactive
protein; and Kaposi's sarcoma-associated herpesvirus (KSHV) viral loads, in patients
with KSHV-associated multicentric Castleman's disease treated with high-dose zidovudine
and valganciclovir, with or without bortezomib or R-EPOCH-R (comprising etoposide,
doxorubicin, vincristine, prednisone, cyclophosphamide, and rituximab) or sirolimus
only, or rituximab in combination with pegylated liposomal doxorubicin hydrochloride,
or observation, or HAART only.

- Correlate laboratory pathogenesis-related parameters with clinical and hematologic
parameters in patients treated with these regimens.

Secondary

- Determine, preliminarily, the therapeutic efficacy and toxicity of high-dose zidovudine
and valganciclovir in these patients.

- Determine, preliminarily, the feasibility of risk-stratifying these patients according
to disease parameters.

- Determine the overall survival of patients treated with these regimens.

- Determine symptom-free and progression-free survival of patients treated with these
regimens.

- Correlate the efficacy of these regimens with disease activity in these patients.

OUTLINE: Patients are assigned to 1 of 6 treatment groups based on disease status.

- Group I (observation only): Patients with asymptomatic disease undergo observation only
or observation in conjunction with highly active antiretroviral therapy (HAART), where
appropriate.

- Group II (high-dose zidovudine [HDAZT] and valganciclovir [VGCV]): Patients with
symptomatic disease that is not life threatening receive oral HDAZT four times daily
and oral VGCV twice daily on days 1-21. Courses repeat every 21 days.

- Group III (bortezomib, HDAZT, and VGCV): Patients with continued symptomatic disease
who are not responding to group II therapy receive bortezomib IV over 3-5 seconds on
days 1, 4, 8, and 11 and HDAZT and VGCV as in group II on days 1-21. Courses repeat
every 21 days.

- Group IV (R-EPOCH-R): Patients with life-threatening disease receive R-EPOCH-R therapy
comprising rituximab IV on days 1 and 5; etoposide IV over 24 hours, doxorubicin IV
over 24 hours, and vincristine IV over 24 hours on days 1-4; oral prednisone once daily
on days 1-5; cyclophosphamide IV over 15 minutes on day 5; and filgrastim (G-CSF) or
pegfilgrastim subcutaneously (SC) once daily beginning on day 6 and continuing until
blood counts recover. Treatment repeats every 21 days for up to 6 courses.

- Group V: Patients in group II or III who do not respond to treatment or patients who
have Kaposi's sarcoma requiring therapy receive rituximab IV and doxorubicin
hydrochloride liposome IV on day 1. Treatment repeats every 21 days for 2-6 courses.
Patients then receive interferon alfa SC 3 times weekly for 4-12 months or HDAZT and
VGCV as in group II.

- Group VI: Patients not responding to HDAZT and VGCV with or without bortezomib, or for
whom other co-morbid conditions require therapy (e.g., Kaposi's sarcoma), or any
disease severity (e.g., performance status) where R-EPOCH-R is considered too toxic,
receive oral sirolimus once daily on days 1-21 in the absence of disease progression or
unacceptable toxicity.

PROJECTED ACCRUAL: A total of 16-30 patients (8-14 for groups II and III and 0-2 for groups
I and IV) will be accrued for this study within 3-5 years.