a study of two associations of rituximab and chemotherapy, with a pet-driven strategy, in lymphoma

Conditions: Lymphoma, B-Cell; Lymphoma, Large-Cell, Diffuse

Summary: this phase ii study randomized r-acvbp and r-chop as induction treatment in patients from 18 to 59 with dlbcl cd20+ lymphoma and 2 or 3 adverse prognostic factors of the age-adjusted ipi. the consolidation treatment is allocated according to the response to induction treatment assessed by pet after the 2nd and 4th induction cycles.

1) induction arm a: 4 cycles of r-acvbp, 2 weeks interval. after the 3rd cycle, if pet 2+ (fixing), collection of peripheral blood stem cell progenitors will be organized at the time of hematological recovery under support with g-csf. the consolidation treatment will depend on results of pet evaluation after cycle 2 (pet2) and cycle 4 (pet4). * consolidation 1a (in case of pet 2- pet 4 -): * high-dose methotrexate with folinic acid rescue; 2 cycles spaced out 14 days. * rituximab-ifosfamide-etoposide : 4 cycles spaced out 14 days * cytarabine sub-cutaneous, during 4 days; 2 cycles spaced out 14 days. * consolidation 2 a (in case of pet 2+ pet4 -): * 2 cycles high-dose methotrexate with folinic acid rescue * high dose with z- beam conditioning regimen followed by autologous transplant. * salvage(in case of pet 4 +): the patient will be treated with a salvage regimen, after a biopsy of the residual mass whenever possible. 2) induction arm b: 4 cycles of r-chop, 2 weeks interval. after the 3rd cycle, if pet 2+ (fixing), collection of peripheral blood stem cell progenitors will be organized at the time of hematological recovery under support with g-csf. the consolidation treatment will depend on results of pet evaluation after cycle 2 (pet2) and cycle 4 (pet4). * consolidation 1b(in case of pet 2- pet 4 -): 4 additional cycles of r-chop, 2-weeks interval * consolidation 2 b(in case of pet 2+ pet 4 -): * 2 cycles high-dose methotrexate with folinic acid rescue * high dose with z- beam conditioning regimen followed by autologous transplant * salvage(in case of pet 4 +): the patient will be treated with a salvage regimen, after a biopsy of the residual mass whenever possible

Eligibility criteria:
inclusion criteria: * patient with histologically proven cd20+ diffuse large b-cell lymphoma (who classification). * age from18 to 59 years, eligible for transplant. * patient not previously treated. * baseline fdg-pet scan (pet0) performed before any treatment with at least one hypermetabolic lesion. * index prognostic factors (ipi) 2 or 3. * with a minimum life expectancy of 3 months. * negative hiv, hbv and hcv serologies £ 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. * poor renal function (creatinin level \>150 mmol/l), poor hepatic function (total bilirubin level \>30 mmol/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. * any serious active disease (according to the investigator's decision). * treatment with any investigational drug within 30 days before planned first cycle of chemotherapy. * pregnant or lactating women or women of childbearing potential not currently practicing an adequate method of contraception * adult patient under tutelage. * impossibility to performed a baseline pet scan (pet0) before randomization and treatment beginning

Keywords: lymphoma pet chemotherapy rituximab