Association of Velcade to R-CHOP in the Treatment of B Cell Lymphoma

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

Sex

All

Minimum age

18 Years

Maximum age

80 Years

Inclusion Criteria:

• Patients with one of the following B-cell Lymphoma CD 20 positive : Mantle cell, Marginal zone, lymphocytic, follicular requiring treatment, Histological transformation from low grade to high grade, diffuse large cell without adverse prognostic factors defined by the international prognostic index (IPI)

* Aged from 18 to 80 years
* Untreated with chemotherapy except with Chlorambucil or Cyclophosphamide per os alone less than 6 months
* Previous radiotherapy except if localized
* Performance status \< 3
* Signed inform consent

Exclusion Criteria:

* Other type of lymphomas: Burkitt, T cell, CD 20 negative
* Central nervous system or meningeal involvement
* Contraindication to any drug contained in the chemotherapy regimen
* HIV disease, active hepatitis B or C
* Treatment with polychemotherapy before except with Chlorambucil or Cyclophosphamide per os less than 6 months
* Prior extended radiotherapy
* Any serious active disease or co-morbid medical condition (according to investigator's decision )
* Renal deficiency (clearance \< 30 ml/mn), liver deficiency (bilirubin \> 30 mmol/l) unless related to lymphoma
* Neuropathy\> grade 2 within 14 days before enrollment
* Platelets \< 30.109/l within 14 days before enrollment
* Neutrophils \< 1.0 109/l within 14 days before enrollment
* Women with pregnancy or without adequate method of contraception
* Any history of active cancer during the last two years

• BACKGROUNDCzuczman MS, Grillo-Lopez AJ, White CA, Saleh M, Gordon L, LoBuglio AF, Jonas C, Klippenstein D, Dallaire B, Varns C. Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy. J Clin Oncol. 1999 Jan;17(1):268-76. doi: 10.1200/JCO.1999.17.1.268. PMID 10458242
• BACKGROUNDCoiffier B, Lepage E, Briere J, Herbrecht R, Tilly H, Bouabdallah R, Morel P, Van Den Neste E, Salles G, Gaulard P, Reyes F, Lederlin P, Gisselbrecht C. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002 Jan 24;346(4):235-42. doi: 10.1056/NEJMoa011795. PMID 11807147
• BACKGROUND44. Marcus R, et al. (2003). An International Multi-Centre, Randomized, Open-Label, Phase III Trial Comparing Rituximab Added to CVP Chemotherapy to CVP Chemotherapy Alone in Untreated Stage III/IV Follicular Non-Hodgkins Lymphoma. Blood, 102, issue 11, (abstract 87).
• BACKGROUNDO'Connor O, Wright J, Moskowitz CH et al. Promising Activity of the Proteasome Inhibitor Bortezomib (Velcade) in the Treatment of Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma. Session Type: Poster Session 517-II. Blood, Volume 102, issue 11, November 16, 2003 (abstract 2346)