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

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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HIV Infections, Giant Lymph Node Hyperplasia

Intervention / Treatment
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* Drug: Rituximab


Participation Criteria
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Eligibility Criteria
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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 Exclusion Criteria: Prior treatment with rituximab Evolutive lymphoma or Kaposi's sarcoma needing treatment Absence of effective contraception Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Rituximab|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained response rate of multicentric Castleman disease at day 60, after 4 infusions of rituximab |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV infections, Giant Lymph Node Hyperplasia, Herpesvirus 8, Human, Rituximab (Mabthera), Antibodies, Monoclonal