Clinical Trial: Rituximab in the Treatment of HIV Associated Multicentric Castleman Disease Dependent on Chemotherapy

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: Multicenter, Phase II Trial Assessing the Efficacy of Rituximab in HIV Infected Patients With Multicentric Castleman Disease Dependent on Chemotherapy (ANRS 117 Study, Cas

Brief Summary: This trial is aimed to study the efficacy of 4 weekly cycles of rituximab in HIV-infected patients with multicentric Castleman disease (giant lymph node hyperplasia) dependent on chemotherapy. Efficacy is assessed by the complete response rate at day 60. The patients are followed until day 365.

Detailed Summary:

HIV-related multicentric Castleman disease (MCD) is a lymphoproliferative disorder characterized by lymphadenopathy with angiofollicular hyperplasia and plasma cell infiltration, associated with KSHV/HHV-8. Patients typically have systemic manifestations such as fever associated with lymphadenopathy, hepatosplenomegaly, respiratory symptoms, peripheral edema, cytopenia, hypergammaglobulinemia, hypoalbuminemia, and high levels of serum C reactive protein (CRP). Symptoms correlate with an important increase of KSHV/HHV-8 DNA in peripheral blood mononuclear cells. HIV-MCD is characterized by a rapidly progressive and often fatal course. HIV-MCD is often refractory to treatment. Vinca alkaloids produce frequent but short-lived responses, and most patients remain dependant upon chemotherapy.

Lymph nodes of patients with HIV-MCD specifically harbor the virus in B cells located in the mantle zone, which stain positively for the CD20 surface antigen. Rituximab, a humanized monoclonal anti-CD20 antibody, has been reported to be effective in some cases, with conflicting data in other cases. The optimal schedule of infusions remains unclear.

Kaposi's sarcoma is often associated with HIV-MCD, and the development of aggressive non-Hodgkin's lymphoma is not a rare outcome.


Sponsor: French National Agency for Research on AIDS and Viral Hepatitis

Current Primary Outcome: Sustained response rate of multicentric Castleman disease at day 60, after 4 infusions of rituximab

Original Primary Outcome: Complete response rate of multicentric Castleman disease at day 60, after 4 infusions of rituximab

Current Secondary Outcome:

  • One-year disease-free survival
  • One-year event-free survival
  • Relapse rate at day 365
  • One-year lymphoma-free survival
  • Tolerance of rituximab
  • One-year overall survival
  • Change in HHV-8 viral load within one year
  • Change in lymphocyte B cell count within one year


Original Secondary Outcome: Same as current

Information By: French National Agency for Research on AIDS and Viral Hepatitis

Dates:
Date Received: August 4, 2005
Date Started: May 2003
Date Completion: January 2006
Last Updated: January 11, 2007
Last Verified: January 2007