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

This study has been terminated.
Sponsor:
Collaborator:
Hoffmann-La Roche
Information provided by:
French National Agency for Research on AIDS and Viral Hepatitis
ClinicalTrials.gov Identifier:
NCT00127569
First received: August 4, 2005
Last updated: January 11, 2007
Last verified: January 2007
  Purpose

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.


Condition Intervention Phase
HIV Infections
Giant Lymph Node Hyperplasia
Drug: Rituximab
Phase 2

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

Resource links provided by NLM:


Further study details as provided by French National Agency for Research on AIDS and Viral Hepatitis:

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

Secondary Outcome Measures:
  • 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

Estimated Enrollment: 25
Study Start Date: May 2003
Estimated Study Completion Date: January 2006
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00127569

Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Hoffmann-La Roche
Investigators
Principal Investigator: Eric Oksenhendler, M.D. AP-HP Hopital Saint-Louis
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00127569     History of Changes
Other Study ID Numbers: ANRS 117 CastlemaB
Study First Received: August 4, 2005
Last Updated: January 11, 2007
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Agency for Research on AIDS and Viral Hepatitis:
HIV infections
Giant Lymph Node Hyperplasia
Herpesvirus 8, Human
Rituximab (Mabthera)
Antibodies, Monoclonal

Additional relevant MeSH terms:
Infection
HIV Infections
Acquired Immunodeficiency Syndrome
Hyperplasia
Giant Lymph Node Hyperplasia
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Pathologic Processes
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Rituximab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 18, 2014