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

Part of paid clinical trials in Bethesda, Maryland.

Sponsor
National Cancer Institute (NCI)
Study ID
NCT00092222
Phase
PHASE2
Status
Active Not Recruiting

Conditions

  • HHV-8
  • HIV
  • Lymphoproliferative Disorder
  • Malignancy

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Etoposide — DRUG
    Etoposide 50 mg/m2 /day continuous intravenous infusion (CIVI) over 24 hours x 4 days (days 1-4) of 21 day cycle. A maximum of 6 cycles of R-EPOCH-R will be administered except in exceptional circumstances.
  • Interferon-alpha — DRUG
    Ages 18 and over: Initial dose of 7.5 million units subcutaneous, three times weekly x 14 days; subsequent dosesincrease dose as tolerated each 14 days to a maximum of 45 million units subcutaneous three times weekly; Ages 12-17: Initial dose of 5 million units/m2 subcutaneous, three times weekly x 14 days Subsequent doses: Increase dose as tolerated each 14 days to a maximum of 30 million units/m2 subcutaneous, three times weekly
  • Rituximab — DRUG
    Rituximab 375 mg/m2 IV day 1, shall be administered prior to Doxil injection. When combined with EPOCH chemotherapy, Rituximab will be given on days 1 and 5.
  • Zidovudine — DRUG
    Cycle 1: Zidovudine 600 mg PO QID x 7-21 days in outpatient setting;600 mg PO q6hours x 7-21 (Intravenous zidovudine 300 mg q 6 hours may be substituted) days for inpatients; Cycle 2 and beyond: 600 mg PO QID x 7 days in outpatient setting; 600 mg PO q 6 hours x 7 days (300 mg q 6 hours may be substituted)
  • Liposomal Doxorubicin — DRUG
    21 day cycle; 20 mg/m2 Liposomal Doxorubicin given on day 1 and shall be administered after completion of Rituximab infusion from 2 to 6 cycles.
  • Bortezomib — DRUG
    1.3 mg/m2 IV days 1, 4, 8, and 11. Cycle length is 21 days.
  • Valganciclovir — DRUG
    Cycle 1: Valganciclovir 900 mg PO BID x 7-21 days in outpatient setting; 900 mg PO q 12 hours x 7-21 days for inpatients; Cycle 2 and beyond: 900 mg PO BID x 7 days for outpatients; 900 mg PO q 12 hours x 7 days (Intravenous ganciclovir 5 mg/kg may be substituted) for inpatients
  • Doxorubicin — DRUG
    10 mg/m2 /day CIVI over 24 hours x 4 days (days 1-4) of 21 day cycle.
  • Vincristine — DRUG
    0.4 mg/m2 /day CIVI over 24 hours x 4 days (days 1-4) of 21 day cycle.
  • Cyclophosphamide — DRUG
    Cyclophosphamide: if CD4 \< 100 cells/mm3, 187 mg/m2 IV (Day 5) if CD4 greater than or equal to 100 cells/mm3, 375 mg/m2 IV (Day 5) of 21 day cycle.
  • Filgrastim (G-CSF) — DRUG
    Filgrastim 300 micrograms subcutaneous daily beginning day 6 until absolute neutrophil count recovery 5000 cells/mm3 (Pegfilgrastim may be substituted with PI approval, at the recommended dose of one 6mg syringe)
  • Prednisone — DRUG
    Prednisone 60 mg/m2/day PO x 5 days (days 1-5)of 21 day cycle.
  • Sirolimus — DRUG
    Maximum daily dose of 40 mg given as a single agent on 21 day cycle.
  • Observation Only — OTHER
    Observation of symptoms

Study Details

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. Participants ages 18 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 participants may take for KSHV-MCD. Zidovudine, or Retrovir(R), 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(TM), 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(TM), 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 gastrointestinal problems and a low blood platelet count. Rituximab and liposomal doxorubicin are drugs given by a catheter into a vein. Interferon-alpha is given by injection into the skin. Those drugs are not experimental, but their use in Castleman's disease is experimental. Some participants may be treated with a combination of chemotherapy followed by interferon-alpha. Interferon-alpha is infected into the skin by a needle. The natural form of interferon is produced by the body and helps to control viral infections. KSHV decreases the effect of the body's interferon, and the researchers want to see if giving higher doses of interferon will help to control KSHV infection. A positron emission tomography (PET) scan, for research purposes only, may be done up to three times a year. A radioactive sugar molecule called fluorodeoxyglucose, or FDG, is used. It is believed that activated lymphocytes that may be found in participants' disease might use more FDG because these cells burn more glucose fuel. This study may or may not have a direct benefit for participants. However, detailed assessments made throughout the study may provide information to help the doctors treat KSHV-MCD better.

Key Dates

Start date
Oct 28, 2004
Status verified
Jun 2026
Primary completion
Oct 1, 2026
Completion
Oct 1, 2026

Study Design

Enrollment
75 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Active Comparator: Active Treament 3
    Patients not responding to high- dose zidovudine and valganciclovir alone may be treated with botezomib plus high- dose zidovudine and valganciclovir
  • Active Comparator: Active Treatment 1
    Single agent sirolimus for patients where targeted oncolytic virotherapy seems suboptimal
  • Active Comparator: Active Treatment 2
    EPOCH chemotherapy with rituximab may be utilized to rescue such patients, with the intent of stabilizing suchpatients
  • Active Comparator: Active Treatment 4
    Rituximab with liposomal doxorubicin (R-Dox) followed by consolidation or lmaintenancel therapy with dose escalating interferon-alpha
  • Active Comparator: Active Treatment 5
    High dose zidovudin and valganciclovir
  • Active Comparator: Natural History
    Observation Only

Primary Outcome Measure

Describe natural history [ Time Frame: Study Closure ]

Locations (1)

FacilityCityStateZIPSite coordinators
National Institutes of Health Clinical CenterBethesdaMaryland20892-

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