Tocilizumab for KSHV-Associated Multicentric Castleman Disease
Condition: Castleman Disease; Multicentric Castleman Disease; Giant Lymph Node Hyperplasia
MeSH terms: Castleman Disease; Lymphadenopathy; Hyperplasia
Intervention: Zidovudine; Tocilizumab; Valganciclovir (VGC)
Intervention description: Zidovudine (AZT) 600 mg orally q6 hours (every 6 hours); Tocilizumab 8mg/kg every 2 weeks; Valganciclovir (VGC) 900 mg orally q12 hours (every 12 hours) on days 1-5 of a 14-day cycle.
Intervention MeSH terms: Zidovudine; Valganciclovir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 8.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Kaposi Sarcoma Herpesvirus; Human Immunodeficiency Virus; Tocilizumab; Multicentric Castleman Disease; Interleukin-6; Castleman Disease; Acquired Immunodeficiency Syndrome (AIDS); Human Herpesvirus-8

Summary:

      Background:

      - Kaposi's sarcoma-associated herpes virus (KSHV)-associated multicentric Castleman disease
      (KSHV-MCD) is caused by a herpes virus known as KSHV. This disease can also cause several
      other cancers, including Kaposi sarcoma. People with KSHV-MCD often have symptoms like fever,
      weight and muscle loss, and fluid in the legs or abdomen. Tocilizumab may be able to block
      the chemicals in the body that cause KSHV-MCD symptoms. Researchers want to test this drug
      and other anti-virus drugs to find the best combination of drugs to treat KSHV-MCD.

      Objectives:

      - To test the effectiveness of tocilizumab with and without other anti-virus drugs for
      KSHV-MCD.

      Eligibility:

      - People at least 18 years of age who have KSHV-MCD and have certain symptoms and blood
      abnormalities caused by their KSHV-MCD.

      Design:

        -  Participants will be screened with a medical history and physical exam. They will also
           have blood tests, and a skin biopsy.

        -  Participants will have tocilizumab injections every 2 weeks for up to 12 weeks. They
           will provide daily blood samples for the first 3 days of treatment.

        -  After the sixth dose, participants will be monitored for 4 weeks to check for possible
           side effects.

        -  Those whose KSHV-MCD does not improve or worsens during the study may have tocilizumab
           combined with two other anti-virus drugs, zidovudine and valganciclovir. These drugs are
           pills that will be taken four times a day for 5 days out of every 2 weeks.

        -  Blood, urine, and saliva samples will be collected throughout the study.
    

Eligibility criteria:

        -  INCLUSION CRITERIA:

          -  Pathologically confirmed Kaposi sarcoma (KS)-associated herpes virus multi-centric
             Castleman disease (KSHV-MCD)

          -  Age greater than or equal to 18

          -  At least one clinical symptom probably or definitely attributed to KSHV-MCD

          -  Intermittent or persistent fever for at least 1 week (>38 degrees C)

          -  Fatigue (Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 or greater)

          -  Gastrointestinal symptoms [includes nausea and anorexia] (CTCAE Grade 1 or greater)

          -  Respiratory symptoms [includes cough and airway hyperreactivity]

        (CTCAE Grade 1 or greater)

          -  At least one laboratory abnormality probably or definitely attributed to KSHVMCD

          -  Anemia (Hgb [men] </=12.5 gm/dL, Hgb [women] </= 11 gm/dL)

          -  Thrombocytopenia (</=130,000/mm(3))

          -  Hypoalbuminemia (<3.4 g/dl)

          -  Elevated C-reactive protein (CRP) (CRP > 3 mg/L)] probably or definitely attributable
             to KSHV-MCD

          -  No life- or organ-threatening manifestations of MCD

          -  Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2

          -  Human Immunodeficiency Virus (HIV)-infected patients should be receiving or willing to
             initiate an effective combination antiretroviral therapy (cART) regimen

          -  Willingness to complete tuberculosis evaluation and start prophylactic
             antituberculosis therapy as soon as is medically feasible if patients have a reactive
             tuberculin skin test and have not completed an adequate course of prevented
             anti-tuberculosis therapy, following American Thoracic Society/ Centers for Disease
             Control recommended guidelines:

        http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5231a4.htm

          -  Ability to understand and willingness to give informed consent

          -  Women of child bearing potential must agree to use birth control for the duration of
             the study

        EXCLUSION CRITERIA:

          -  Uncontrolled bacterial, mycobacterial, or fungal infection

          -  Uncontrolled intercurrent illness including, symptomatic congestive heart failure,
             unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations
             that would limit compliance with study requirements or ability to receive therapy.

          -  Pregnant or lactating women

          -  Any abnormality that would be scored as National Cancer Institute (NCI) Common
             Toxicity Criteria (CTC) Grade 3 toxicity that is unrelated to HIV, its treatment, or
             to MCD that would preclude protocol treatment. Exceptions include:

          -  Lymphopenia

          -  Direct manifestations of Kaposi sarcoma or MCD

          -  Direct manifestation of HIV (i.e. low cluster of differentiation 4 (CD4) count)

          -  Direct manifestation of HIV therapy (i.e. Hyperbilirubinemia associated with protease
             inhibitors)

          -  Asymptomatic hyperuricemia

          -  Hypophosphatemia

          -  Elevated creatine kinase (CK) attributed to exercise

          -  Past or present history of malignant tumors other than Kaposi sarcoma unless one of
             the following:

          -  Complete remission for greater than or equal to 1 year from completion of therapy

          -  Completely resected basal cell carcinoma

          -  In situ squamous cell carcinoma of the cervix or anus

          -  Patients with concurrent Kaposi sarcoma requiring immediate cytotoxic chemotherapy

          -  History of tocilizumab therapy within prior three months

          -  History of rituximab or bevacizumab therapy within three months

          -  History of greater than or equal to 2 allergic reaction or any grade anaphylactic
             reaction during prior administration of tocilizumab