Phase III multicentric IIL study, three randomized arms (R-CVP vs R-CHOP vs R-FM),for treatment of patients with stage II-IV follicular lymphoma

INTERVENTION: Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Rituximab CAS Number: 174722‐31‐7 Concentration unit: mg milligram(s) Concentration number: 375‐ Trade Name: VINCRISTINA PHARMACIA & U.*1MG Pharmaceutical Form: Solution for infusion INN or Proposed INN: Vincristine CAS Number: 2068‐78‐2 Concentration unit: mg milligram(s) Concentration number: 1‐ Trade Name: DELTACORTENE*20CPR 5MG Pharmaceutical Form: Soluble tablet INN or Proposed INN: Prednisone CAS Number: 53‐03‐2 Concentration unit: mg milligram(s) Concentration number: 40‐ Trade Name: ENDOXAN BAXTER*50CPR RIV 50MG Pharmaceutical Form: Powder for solution for injection INN or Proposed INN: Cyclophosphamide CAS Number: 6055‐19‐2 Concentration unit: mg milligram(s) Concentration number: 750‐ Trade Name: ADRIBLASTINA*EV FL 10MG+F 5ML Pharmaceutical Form: Powder and solvent for solution for injection INN or Proposed INN: Doxorubicin CAS Number: 25316‐40‐9 Concentration unit: mg milligram(s) Concentration number: 50‐ Trade Name: FLUDARA*20CPR RIV 10MG Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: Fludarabine CAS Number: 75607‐67‐9 Concentration unit: mg milligram(s) Concentration number: 25‐ Trade Name: ONKOTRONE*EV 1FL 10MG 5ML Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Mitoxantrone CAS Number: 70476‐82‐3 Concentration unit: mg milligram(s) Concentration number: 10‐ CONDITION: Stage II‐IV Follicular Lymphoma ; MedDRA version: 14.1 Level: PT Classification code 10016897 Term: Follicle centre lymphoma diffuse small cell lymphoma recurrent System Organ Class: 10029104 ‐ Neoplasms benign, malignant and unspecified (incl cysts and polyps) Therapeutic area: Diseases [C] ‐ Blood and lymphatic diseases [C15] PRIMARY OUTCOME: Main Objective: Assessment of the Time to Treatment Failure (TTF)in patients treated with R‐CVP, R‐CHOP and R‐FM. Primary end point(s): to assesment survival, toxicity , clinical and molecolar responses after one cycle of patients treatment Secondary Objective: ‐ Assessment of Overall Survival (OS)in patients treated with R‐CVP, R‐CHOP and R‐FM. ‐ Assessment of Progression Free Survival (PFS)in patients treated with R‐CVP, R‐CHOP ‐ Assessment of Duration of Response (DR)in patients treated with R‐CVP, R‐CHOP and R‐FM. ‐ Assessment of Response Rate(RR) in patients treated with R‐CVP, R‐CHOP and R‐FM. ‐ Assessment of molecular Response Rate in patients treated with R‐CVP, R‐CHOP and R‐FM. ‐ Assessment of toxicity of R‐CVP, R‐CHOP, R‐FM treatments. INCLUSION CRITERIA: 1.Histological DIAGNOSIS of B cell FOLLICULAR LYMPHOMA 2. ECOG performance status 0‐2 3. Age range 18‐75 4. Ann Arbor Stage: II‐IV 5. assessment of pathology with diagnostics biopsy 6. Presence of one of these criteria: a)B Sistemic symptoms B b)extranodale pathology c)cytopenia d)splenomegaly e)leukemia f)SEROUS EFFUSION g)ves>20 mm/h h)ldh >normal value i)nodale or extranodal mass > 7 cm j)3 or more nodal sites >3 cm k)adenopatic syndrome 7.LVEF> 50% 8.Normal hepatic (bilirubin <1.5 mg/dl) and renal functionality (creatinin < 2mg/dl). If there is a lymphoma it's allow values of bilirubin >1.5 mg/dl and of creatinin > 2mg/dl. 9.No previous treatment for follicolar lymphoma unless RT‐IF 10.lifetime > 6 mounth 11.Absence of HbsAg, HCV e HIV. 12.negative Coombs Test 13.negative pregnant test 14.cotracceptive method during the treatment and the follow three months. 15. formal written consent 16.Ability to follow the p