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

Phase 2

Terminated

• Conditions: HIV Infections; Giant Lymph Node Hyperplasia

• Registration Number: NCT00127569
• Lead Sponsor: French National Agency for Research on AIDS and Viral Hepatitis

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 Description

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.

Study Timeline

• Study Start: 2003-05
• Study First Submitted: 2005-08-04
• Study First Submitted QC: 2005-08-04
• Study First Posted: 2005-08-08
• Study Completion: 2006-01
• Status Verified: 2007-01
• Last Update Submitted: 2007-01-11
• Last Update Posted: 2007-01-12

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

• Confirmed multicentric Castleman disease, with dependence on vinblastine or VP16 for at least 3 months, whenever they have been splenectomized
• At least one Castleman crisis since onset of chemotherapy
• Ongoing highly active antiretroviral therapy (HAART) for at least 3 months
• No threshold of CD4 cell count and HIV-RNA
• Signed written informed consent

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Exclusion Criteria

• Prior treatment with rituximab
• Evolutive lymphoma or Kaposi's sarcoma needing treatment
• Absence of effective contraception
• Pregnancy

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Sustained response rate of multicentric Castleman disease at day 60, after 4 infusions of rituximab

Secondary Outcome Measures

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