Bethesda, Maryland 20892

  • Sarcoma

Purpose:

RATIONALE: Kaposi's sarcoma-associated herpesvirus (KSHV) can cause several kinds of cancer and lymphoproliferative disorders, including some forms of Castleman's disease. Antiviral drugs such as zidovudine and valganciclovir act against KSHV. Bortezomib may make virus cells more sensitive to zidovudine and valganciclovir. Combining zidovudine and valganciclovir with or without bortezomib may kill more KSHV cells and may be an effective treatment for KSHV-associated Castleman's disease. Alternatively, the use of combination chemotherapy and monoclonal antibody therapy using rituximab or sirolimus alone may be effective in treating patients who have life-threatening KSHV-associated Castleman's disease. PURPOSE: Clinical trial to study the effectiveness of antiretroviral therapy with or without bortezomib or combination chemotherapy and rituximab or sirolimus only or observation only in treating patients who have KSHV-associated Castleman's disease.


Study summary:

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.


Criteria:

DISEASE CHARACTERISTICS: - Histologically confirmed Kaposi's sarcoma-associated herpesvirus-associated multicentric Castleman's disease PATIENT CHARACTERISTICS: Age - 12 and over Performance status - ECOG 1-4* (groups II and III only) - ECOG 4 (group IV only) NOTE: *ECOG 4 eligible for groups II or III only if disease was refractory to prior conventional cytotoxic chemotherapy with rituximab Life expectancy - Not specified Hematopoietic - Not specified Hepatic - Not specified Renal - Not specified Other - Not pregnant or nursing - Negative pregnancy test - No grade IV toxicity unrelated to HIV, its treatment, or multicentric Castleman's disease that would preclude study therapy - No other malignancy requiring concurrent treatment that would preclude study therapy or monitoring - No other condition or circumstance that would preclude study participation PRIOR CONCURRENT THERAPY: Biologic therapy - Not specified Chemotherapy - Not specified Endocrine therapy - Not specified Radiotherapy - Not specified Surgery - Not specified


NCT ID:

NCT00099073


Primary Contact:

Study Chair
Robert Yarchoan, MD
NCI - HIV and AIDS Malignancy Branch


Backup Contact:

N/A


Location Contact:

Bethesda, Maryland 20892
United States

Robert Yarchoan, MD
Phone: 301-496-8959

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: February 03, 2023

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