Association of Velcade to R-CHOP in the Treatment of B Cell Lymphoma
Condition: B Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, B-Cell
Study type: Interventional
Phase: Phase 2

Summary: 
      The primary objective of this study is to evaluate the response rate and toxicity of the
      association R-CHOP with two schedules of administration of Velcade, in B-cell CD 20 +
      lymphoma patients, aged from 18 to 80 years

      The goal is to get a response rate at least at what observed with R-CHOP alone and will be
      evaluates with a sequential test.

      The other objective is to evaluate the toxicity
    

Detailed description: 
      The association of the monoclonal antibody Rituximab to chemotherapy regimen of B-cell
      lymphoma is associated with an increase response rate and event free survival when compared
      to chemotherapy alone (Coiffier et al NEJM 2002). It has been observed in almost all
      histological type of B-cell lymphomas. No significant increase of toxicity was observed
      especially in the most used regimen CHOP and the association R-CHOP is a standard for most
      B-cell malignancies CD20 positive.

      However, in patients with diffuse large cell lymphoma progress should be made as the complete
      response rate is below 75% in most situation and in low grade lymphoma, although patients
      respond well to chemotherapy complete remission rate averaged generally 50% (Marcus et al
      2003), Czuczman et al 1999) .

      There is a need to improve this association with new innovative agent. Before running
      randomized study it is important to evaluate the like hood of getting improvement by phase 2
      study testing tolerance and efficacy on a well established regimen.

      Bortezomib (Velcade formerly PS 341) is a proteasome inhibitor which has shown promising
      activity in the treatment of refractory myeloma. As single agent in indolent lymphomas,
      administered twice per weeks for 2 weeks followed by one week rest period it has already
      showed activity in phase 2 study. It is well tolerated and main toxicity was neuropathy and
      thrombocytopenia.

      Proteasome inhibitors can act through multiple mechanisms to arrest tumor growth, tumor
      spread, and angiogenesis. In vitro studies have shown a synergistic effect of the association
      of Velcade and doxorubicin on myeloma cell lines resistant to chemotherapy.

      Association of Velcade to standard chemotherapy regimen is under study with the aim of
      improving on the results.

      Association of Velcade to one of the most efficient treatment of B-cell lymphoma, R-CHOP,
      might increase the response rate.

      However, different schedules should be explored in order to better appreciate efficacy and
      toxicity.

      This randomized phase 2 study is designed to evaluate the response rate and the toxicity of
      two schedules of administration of Velcade in association with R-CHOP. The aim of the study
      is to establish a well tolerated regimen giving a response rate in the limit upper/lower of
      what is observed with conventional R-CHOP used in all the different histological subtypes of
      B cell lymphomas patients requiring treatment.

      The heterogeneity of the population will preclude any meaningful subgroup analysis.

      It is important to evaluate tolerability before exploring the efficacy of this new regimen in
      large randomized studies or in specific phases II study which will need 50 patients for each
      subgroup of patients.
    

Intervention name(s): Rituximab -CHOP plus Velcade
Intervention type(s): Drug
Intervention MeSH terms: Rituximab; Bortezomib
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: B Lymphoma; Velcade; Chemotherapy