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

HIV Infections Clinical Trial

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, CastlemaB)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00127569
• Other study ID #: ANRS 117 CastlemaB
• Status: Terminated
• Phase: Phase 2
• First received: August 4, 2005
• Last updated: January 11, 2007
• Start date: May 2003
• Est. completion date: January 2006

Study information

• Verified date: January 2007
• Source: French National Agency for Research on AIDS and Viral Hepatitis
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 25
• Est. completion date: January 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Giant Lymph Node Hyperplasia
• HIV Infections
• Hyperplasia

Intervention

Drug:
• Rituximab

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
French National Agency for Research on AIDS and Viral Hepatitis	Hoffmann-La Roche

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained response rate of multicentric Castleman disease at day 60, after 4 infusions of rituximab
Secondary	One-year disease-free survival
Secondary	One-year event-free survival
Secondary	Relapse rate at day 365
Secondary	One-year lymphoma-free survival
Secondary	Tolerance of rituximab
Secondary	One-year overall survival
Secondary	Change in HHV-8 viral load within one year
Secondary	Change in lymphocyte B cell count within one year