acvbp plus rituximab versus chop plus rituximab in patients with diffuse large b-cell lymphoma and age-adjusted ipi of 1

Conditions: Diffuse Large-Cell Lymphoma

Summary: this study is a multicentric randomized trial evaluating the efficacy of the combination acvbp+rituximab compared to the combination of chop+rituximab in patients aged from 18 to 59 years with diffuse large b-cell lymphoma and one factor of the age-adjusted international prognostic index (ipi).

this phase iii multicentric open label randomized study is based on the results of previous lnh 93-5 and lnh98-5 studies. the lnh93-5 study has shown that the acvbp regimen gave a longer efs (39% vs 29% at 5 years, p=0.005) and a longer overall survival (46% vs 38% at 5 years, p=0.036) than chop in patients aged between 61 and 69 with an ipi score ≥1. however acvbp had a more important toxicity and a higher treatment related mortality (13% vs 7%, p\<0.01), specially after 65 years. in younger patients acvbp is better tolerated. the addition of rituximab to standard chop (r-chop) has been shown in lnh98-5 study to improve complete remission rate (cr), event-free survival (efs) and overall survival (os) in elderly patients with b-dlcl. considering only patients with an aa-ipi score of 1, the 2 year efs was 75% in the r-chop group as compared with 42% in the chop group. this study is designed to test whether addition of rituximab to acvbp is better than r-chop in patients younger than 60. primary endpoint is event-free survival, we expect a gain in 2 years-efs of 10% in r-acvbp group as compared with r-chop group. this study is a multicentric, phase iii open-label, randomized trial evaluating the efficacy of acvbp+rituximab compared to chop+rituximab in patients aged from 18 to 59 years with non previously treated diffuse large b-cell lymphoma and one factor of the age-adjusted international prognostic index

Eligibility criteria:
inclusion criteria: patient with histologically proven cd20+ diffuse large b-cell lymphoma (who classification) aged from 18 to 59 years. age-adjusted international prognostic index equal to 1 (elevated ldh level or stage iii-iv or ecog status 2-3-4). patient not previously treated. with a minimum life expectancy of 3 months. negative hiv, hbv and hcv serologies test 4 weeks (except after vaccination). having previously signed a written informed consent. exclusion criteria: any other histological type of lymphoma. any history of treated or non-treated indolent lymphoma. however, patients not previously diagnosed and having a diffuse large b-cell lymphoma with some small cell infiltration in bone marrow or lymph node may be included. central nervous system or meningeal involvement by lymphoma. contra-indication to any drug contained in the chemotherapy regimens. any serious active disease (according to the investigator's decision). poor renal function (creatinin level\>150µmol/l), poor hepatic function (total bilirubin level\>30mmol/l, transaminases\>2.5 maximum normal level) unless these abnormalities are related to the lymphoma. poor bone marrow reserve as defined by neutrophils \<1.5 g/l or platelets \<100 g/l, unless related to bone marrow infiltration. any history of cancer during the last 5 years with the exception of non-melanoma skin tumors or stage 0 (in situ) cervical carcinoma. treatment with any investigational drug within 30 days before planned first cycle of chemotherapy and during the study. pregnant or lactating women. adult patient under tutelage.

Keywords: lymphoma, diffuse large b-cell rituximab chemotherapy