Clinical Trial: Tocilizumab for KSHV-Associated Multicentric Castleman Disease

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Pilot Study of Tocilizumab in Patients With Symptomatic Kaposi Sarcoma Herpesvirus (KSHV) - Associated Multicentric Castleman Disease

Brief Summary:

Background:

- 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 w
  

  Detailed Summary:

  BACKGROUND:

  • Kaposi sarcoma herpesvirus-associated multicentric Castleman disease (KSHVMCD) is a rare lymphoproliferative disorder that develops predominantly in HIVinfected patients. Patients often have symptoms from interleukin-6 (IL-6), KSHVencoded viral IL-6 (vIL-6), and other cytokines
  • Goals of therapy include rapid resolution symptoms and elimination of reservoirs of KSHV-infected plasmablasts.
  • Tocilizumab is a humanized anti-IL-6 receptor (gp80) antibody with activity against MCD unrelated to KSHV (KSHV-negative MCD). While tocilizumab does not directly affect vIL-6 signaling or other KSHV driven pathologic processes, IL-6 overproduction plays a major role in symptoms in KSHV-MCD, and blocking IL-6 may be sufficient to treat this disorder by blocking autocrine and paracrine stimulation. Combination with zidovudine (AZT) and valganciclovir (VGC), agents that target KSHV replication, have virus-activated cytotoxic activity, and are active in KSHV-MCD may be useful and necessary in some patients.

  OBJECTIVES:

  • Primary objective: Estimate clinical benefit of tocilizumab 8mg/kg every 2 weeks for up to 12 weeks in patients with symptomatic KSHV-MCD using a modified KSHVMCD Clinical Benefit Response Criteria
  • Secondary objectives:
  • Estimate best clinical, biochemical, radiographic, and overall responses in patients with KSHV-MCD treated for up to 12 weeks with tocilizumab 8mg/kg every 2 weeks using the prior NCI KSHV-MCD Response Criteria.
  • In patients with inadequate response to tocilizumab monotherapy: explore preliminarily the activity
    Sponsor: National Cancer Institute (NCI)
    

    Current Primary Outcome: Determine the efficacy of tocilizumab in the treatment of KSHV-MCD. [ Time Frame: Evaluation of MCD clinical and biochemical response at each visit. ]
    
    

    Original Primary Outcome: Estimate clinical benefit of tocilizumab 8mg/kg every 2 weeks for up to 12 weeks in patients with symptomatic KSHV-MCD using a modified KSHV-MCD Clinical Benefit Response Criteria [ Time Frame: 4 years ]
    
    

    Current Secondary Outcome:

    • Estimate best clinical, biochemical, radiographic and overall response. [ Time Frame: Clinical and laboratory responses are assessed in aggregate and compared to baseline. ]
    • Evaluate progression-free and overall survival with tocilizumab and tocilizumab/AZT/VGC. [ Time Frame: Time interval from the date of enrollment to the date of progression from best response. ]
    • Evaluate safety and tolerability of tocilizumab alone and in combination with AZT/VGC [ Time Frame: Toxicities will be evaluated both per cycle and per patient. ]
    • Evaluate the effect of tocilizumab on the pharmacokinetics of antiretroviral agents that are CYP3A4 substrates in patients with symptomatic KSHVMCD [ Time Frame: Cycle 1, Day 1, Day 3, Cycles 2--6 ]
    • Evaluate effect of tocilizumab on KS [ Time Frame: Baseline, week 7 and at off-study ]
    
    
    

    Original Secondary Outcome:

    • Estimate radiographic responses [ Time Frame: 4 years ]
    • Explore activity of tocilizumab combined with AZT/VGC [ Time Frame: 4 years ]
    • Evaluate safety and tolerability [ Time Frame: 4 years ]
    • Evaluate effect of tocilizumab on PK of select antiretronial agents. [ Time Frame: 4 years ]
    
    
    Information By: National Institutes of Health Clinical Center (CC)
    

    Dates:
    Date Received: September 24, 2011
    Date Started: August 6, 2011
    Date Completion: July 1, 2020
    Last Updated: May 12, 2017
    Last Verified: January 6, 2017