R-CHOP-14 Versus R-CHOP-21 and Darbepoetin Alpha in Patients Aged 60-80 Years With Diffuse Large B-cell Lymphoma
Condition: Diffuse Large Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Large B-Cell, Diffuse
Study type: Interventional
Phase: Phase 3

Summary: 
      This study is a multicentric randomized trial evaluating the efficacy and safety of R-CHOP
      given every 14 days compared to R-CHOP given every 21 days in association or not with
      darbepoetin alfa in order to maintain hemoglobin above 13 g/dl, compared to classical
      symptomatic treatment of anemia in patients aged from 60 to 80 years with diffuse large
      B-cell lymphoma.
    

Detailed description: 
      In patients aged 60 to 75 years with diffuse large B-cell lymphoma, the shortening of
      interval between the courses of CHOP combination (CHOP-14), improves the complete response
      rate, the progression free survival and the overall survival.

      The addition of Rituximab to standard CHOP (R-CHOP) has also been shown to improve complete
      remission rate (CR), event-free survival (EFS) and overall survival (OS) in elderly patients
      with B-DLCL.

      The aim of this study is to test the hypothesis that the increase of the dose intensity by
      shortening the interval between two courses of R-CHOP (R-CHOP-14)could further improve the
      results of the R-CHOP.

      Anemia is frequent at diagnosis and during the treatment of aggressive lymphoma. In the
      previous LNH 98-5 study, 72 % of the patients had, at the diagnosis, a hemoglobin level
      inferior to 13 g/dl. Moreover, during the treatment, 92 % of the patients had a hemoglobin
      level less than 13 g/dl and 30 % were transfused. The presence of anemia at diagnosis is an
      indicator of poor prognosis in multivariate analysis. This prognosis impact could probably be
      explained at cellular level on the tumor. Tumoral hypoxia is increased by the presence of
      anemia. Due to this hypoxia, the expression of tumor growth factor may be increased: e.a VEGF
      and the induction of expression of multi drug resistance (MDR1) is observed. This resistance
      to treatment is also due to the inhibition of genotoxic activity of free radicals induced by
      ionised radiation and chemotherapy. Experimentally, the negative impact of hypoxia on the
      efficacy of chemotherapy has been demonstrated in sarcoma cell lines for doxorubicin,
      vincristine and all most cyclophosphamide. Finally, hypoxia induced over expression of
      apoptosis resistance genes and induced a growth advantage for apoptosis resistant tumoral
      lines. Improvement of survival in patients receiving erythropoetin with chemotherapy or
      radiotherapy was suggested in a study on patients treated with a neoadjuvant
      radiochemotherapy for head and neck cancer. Erythropoetin could act to protect several normal
      tissues during chemotherapy and thus could decrease treatment related morbidity. Darbepoetin
      alfa is a new recombinant protein stimulating erythropoiesis. Thus, the use of darbepoetin
      alfa, in association with chemotherapy, could increase CR rate, EFS and OS in patients
      treated for diffuse large B-cell lymphoma.

      This study is a multicentric, phase III open-label, randomized trial evaluating the efficacy
      and safety of R-CHOP given every 14 days compared to R-CHOP given every 21 days in
      association or not with darbepoetin alfa in order to maintain hemoglobin above 13 g/dl,
      compared to classical symptomatic treatment of anemia in patients aged 66 to 80 years with
      not previously treated diffuse large B-cell lymphoma with at least one adverse prognostic
      factor of the age adjusted IPI.
    

Intervention name(s): Darbepoetin alfa
Intervention type(s): Drug
Intervention description(s): prophylactic administration of darbepoetin alfa in experimental arm
Intervention MeSH terms: Darbepoetin alfa
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: lymphoma, diffuse large B-cell; rituximab; chemotherapy; erythropoetin; darbepoetin alfa