Metronomic Chemotherapy in Elderly Non-fit Patients With Aggressive B-Cell Lymphomas

This is a phase II study of metronomic chemotherapy in elderly non-fit patients (\>65 years) with aggressive B-Cell lymphomas

Patients eligible for the study will receive 6 courses (q 28 days) of the DEVEC combination, according to the following schedule: * DE: Prednisone (Deltacortene) 25 mg /day will be orally administered from day 1 to day 28 only in cycle 1 From cycle 2 to 6 it is reduced to three times a week (after breakfast, MON, WED, FRI) * V: Vinorelbine 30 mg/day will be orally administered three times a week, 3 week on and 1 week off (after breakfast, MON, WED, FRI). * E: Etoposide 50 mg/day will be orally administered from day 1 to day 14 (before lunch). * C: Cyclophosphamide 50 mg/day will be orally administered from day 1 to day 21 (after dinner). * Rituximab: 375 mg/m2 will be administered by IV infusion up to four infusions on days 8, 15, 22, 29, only in patients suitable for infusion treatment and relapsed after \>6 months from last R-chemotherapy. Refractory patients who had received at least 5 doses of Rituximab will not repeat it during the metronomic therapy. Super-frail patients will not receive etoposide during cycles 1 and 2; etoposide will be included in the treatment schedule starting from cycle 3 at reduced dose (50 mg/day, from day 1 to day 7) only in patients who in cycles 1 and 2 didn't experience hematological toxicity \>G2 and/or non-hematological toxicity \>G1. In Unfit and Frail patients with hemoglobin level at study entry \<11 gr/dL, will start etoposide will be orally administered at reduced dose (50 mg/day from day 1 to day 7). If hemoglobin will raise to ≥11 gr/dL, at subsequent induction cycles etoposide will be administered at full dose (50 mg/day, from day 1 to day 14), As a preventive measure, to avoid perforation, patients with gastrointestinal visceral involvement will receive a pre-phase therapy with steroids (prednisolone 40mg/m2 ) for 6-7 days before starting protocol treatment. Moreover, in these patients the four Rituximab doses will be administered in cycle 2. Patients in CR, CRu, PR and SD after 2 cycles will continue with additional 4 courses. At the end of the induction phase patients in CR, CRu and PR (and also in SD at discretion of local investigator) will continue treatment with maintenance therapy including Vinorelbine, Cyclophosphamide, and Prednisone oral combination to be repeated every 28 days for up to 6 cycles, according to the following schedule: * Cyclophosphamide 50 mg/day will be orally administered from day 1 to day 14 (after dinner). * Vinorelbine 30 mg/day will be orally administered three times a week, 3 week on and 1 week off (after breakfast, MON, WED, FRI). * Prednisone 25 mg/day will be orally administered twice a week (after breakfast, MON, FRI). Patients in CR/CRu at the EOT can continue with a post-maintenance phase at discretion of the local investigator up to 12 months, progression or inacceptable toxicity, according to following schedule: * Vinorelbine 30 mg/day will be orally administered three times a week, 3 week on and 1 week off (after breakfast, MON, WED, FRI). * Prednisone 25 mg/day will be orally administered twice a week (after breakfast, MON, FRI). Patients with evidence of Progressive Disease (PD) at any point will stop treatment.