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

French National Agency for Research on AIDS and Viral Hepatitis

Status and phase: Terminated; Phase 2

Conditions: Giant Lymph Node Hyperplasia; HIV Infections

Treatments: Drug: Rituximab

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT00127569

ANRS 117 CastlemaB

Details and patient eligibility

About

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.

Full 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.

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)