R-ICE Versus R-DHAP in Patients Aged 18-65 With Relapse Diffuse Large B-cell Lymphoma
Condition: Lymphoma, Large-Cell, Diffuse
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Study type: Interventional
Phase: Phase 3

Summary: 
      The primary objective of this study is to evaluate the efficacy and safety of induction
      therapy R-ICE in comparison to R-DHAP after 3 cycles adjusted to successful mobilization of
      stem cells in patients with previously treated diffuse large B-cell lymphoma CD20.

      The goal is to detect a difference in mobilization adjusted response rate of 15% between
      R-ICE and R-DHAP.

      The other objective is to evaluate the efficacy and safety of MabThera maintenance therapy
      after transplantation as measured by the event free survival.

      The goal is to obtain a 15% increase of event free survival at 2 years.
    

Detailed description: 
      In vitro, the addition of rituximab to standard anticancer drugs increases cell lyses even in
      chemoresistant cell lines. This chemosensitization effect was also demonstrated in vivo by
      the results of the GELA trial in elderly patients with DLCL. Reported phase II study results
      on the RICE regimen for treatment of patients with relapsed DLCL and comparison with
      historical controls being treated with ICE suggests that this effect (15% improvement in
      response rate) is likely in relapsing DLCL and had led the SWOG to stop a randomized trial
      comparing ICE vs RICE in patients with relapsed aggressive lymphoma.

      In the setting of relapsed DLCL, high dose therapy (HDT) followed by autologous stem cell
      transplantation (ASCT) remains the standard to improve survival in highly selected
      chemosensitive patients. In the Parma study, only 58% of the patients with relapsed
      aggressive NHL were good responders after DHAP and 24% were in complete remission. Moreover,
      the quality of response depended on prognostic factors such as IPI and relapse > 12 months
      after treatment, and only patients responding to salvage therapy benefited from HDT + ASCT.
      As shown in the PARMA study. The goal in relapsed DLCL is to improve complete response rates
      before transplantation as it is the main parameter for eligibility for HDT + ASCT and the
      main prognostic factor. Unlike first line treatment with CHOP, no standard chemotherapy
      exists for relapsing patients. DHAP has been the most frequently used regimen for decades but
      incorporates only two drugs, and has dose-limiting renal toxicity. The ICE regimen was
      developed at several dosages and studies consistently produced CR rates that were 10-15%
      superior to DHAP. It is expected that this difference will remain the same with the addition
      of rituximab to both regimens. Recent phase II data in patients with relapsed DLCL not
      previously treated with rituximab showed that RICE produced a response rate of 78% with a
      complete remission rate of 58% and was active in primary refractory disease as well as in
      intermediate-high risk patients (IPI 2-3). Association of DHAP to Rituximab, R-DHAP has been
      done on small series of patients by investigators, including patients relapsing after
      autotransplant. Despite numerous phase II studies, no randomized study has been performed
      comparing the two regimens (DHAP/ICE) or others in relapsing DLCL. Treatment of first line
      DLCL has been changed in the past 10 years with more intensive regimens, often followed by
      ASCT, and very recently with the addition of rituximab to chemotherapy and therefore the
      population of relapsing patients might be different from the one in the initial PARMA study.
      A large lymphoma intergroup study working on a large prospective data base might help to find
      the best salvage regimen and to assess the role of retreatment with monoclonal antibodies in
      these patients. Finally, the role of rituximab maintenance therapy after HDT + ASCT in
      prolonging second complete response should be evaluated.
    

Intervention name(s): Rituximab; Etoposide; Carboplatine; Ifosfamide + Mesna; Cisplatine; Cytosine Arabinoside; Dexamethasone; Autologous Stem Cell Transplantation; BCNU; Etoposide; Cytarabine; Melphalan
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Procedure; Drug; Drug; Drug; Drug
Intervention description(s): 375 mg/m² D-2/D1; 100 mg/m² D1-D2-D3; max 800mg D2; 5 g/m² from D2 to D13; 100 mg/m² from D1 to D13; 2000 mg/m²/12 h D2 D3; 40 mg From D1 to D4; 300mg/m² on D-6; 200 mg/m² from D-6 to D-3; 100 mg/m² from D-6 to D-3; 140 mg/m² on D-2
Other intervention name(s): R; ASCT; BICNU
Intervention MeSH terms: Cytarabine; Dexamethasone; Rituximab; Etoposide; Etoposide phosphate; Melphalan; Ifosfamide; Carboplatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Lymphoma; Chemotherapy; rituximab