A Phase II Study for Patients With Indolent Non-follicular Non-Hodgkin's Lymphoma

This is a prospective, multicenter phase II trial designed to determine efficacy and safety of a chemoimmunotherapy with the combination of Bendamustine + Rituximab in patients with advanced untreated Indolent non Follicular non-Hodgkin Lymphomas (INFL).

The study includes and induction phase and a consolidation phase.

Inclusion criteria

• Understand and voluntarily sign an informed consent form
• Histological (bone marrow or lymph nodes biopsy) proven diagnosis of B-cell CD20- positive non-follicular NHL according to REAL/WHO Classification:

i. small lymphocytic lymphoma-SLL (bone marrow or lymph nodes biopsy ii. lymphoplasmacytic/citoid lymphoma/ Waldenstrom macroglobulinemia(bone marrow or lymph nodes biopsy) iii. nodal marginal zone lymphoma (lymph nodes biopsy)

• Untreated patients
• Stage III or IV or stage II with more than three involved sites
• Presence of at least one of the following criteria for the definition of active disease:

• Systemic symptoms
• Hemoglobin less than 10 g/dL (due to lymphoma)
• Platelets less than 100 x 10 9/L (due to lymphoma)
• Diffuse bone marrow infiltrate
• Lymphocyte doubling time less than 12 months (in leukemic cases)
• Bulky disease (>7 cm)
• Aged 18 - 75 Life expectancy >6 months
• ECOG performance status 0-2
• LVEF ≥45% or FS ≥37%
• ANC ≥1 x 10 9/l and Platelets count ≥75 x 10 9/l, unless due to bone marrow involvement by follicular lymphoma
• Creatinine up to 1.5 x ULN
• Conjugated bilirubin up to 2 x ULN
• Alkaline phosphatase and transaminases up to 2 x ULN
• Written informed content

Exclusion criteria

• Patients with diagnosis of marginal zone lymphoma of splenic or MALT origin
• Patients with diagnosis of typical Chronic Lymphocytic Leukemia (CLL)
• Men not agreeing to take adequate contraceptive precautions during and for at least 6 months after cessation of therapy
• History of other malignancies within 3 years prior to study entry except for: adequately treated carcinoma in situ of the cervix; basal or squamous cell skin cancer; low grade, early stage, localized prostate cancer treated surgically with curative intent; good prognosis DCIS of the breast treated with lumpectomy alone with curative intent
• Medical condition requiring long term use (>1 months) of systemic corticosteroids
• Active bacterial, viral, or fungal infection requiring systemic therapy
• Concurrent medical condition which might exclude administration of therapy
• Cardiac insufficiency (NYHA grade III/IV)
• Myocardial infarction within 6 months of entry on study
• Severe chronic obstructive pulmonary disease with hypoxemia
• Severe diabetes mellitus difficult to control with adequate insulin therapy
• Hypertension that is difficult to control
• Impaired renal function with creatinine clearance <30 ml/min
• HIV positivity
• HBV positivity with the exception of patients HbsAg negative and Ab anti-Hbcore positive(these patientes need to receive prophylaxis with Lamivudine)
• HCV positivity with the exception of patients with HCV RNA negative.
• CNS involvement by lymphoma
• Participation at the same time in another study in with investiogational drugs are used
• Known hypersensitivity or anaphylactic reactions to murine antibodies or proteins
• Any other co-existing medical or psychological condition that would preclude participation in the study or compromise ability to give informed consent
• Women in pregnancy or breastfeeding