The objective of the study is to demonstrate the safety, tolerability, and activity of Rituximab-Bendamustine-Cytarabine(R-BAC) regimen in patients with mantle cell lymphoma (MCL) aged 65 years or more, as well as in younger patients who are not eligible for intensive regimens including/not including autologous transplantation.

Since Bendamustine has recently shown promising safety and efficacy in combination with monoclonal antibodies in the treatment of patients with MCL, the goal of this study is to investigate the possible therapeutic benefit of combining Ara-C with Bendamustine and Rituximab (R-BAC). All three agents exhibit individual and unique mechanisms of action in MCL, and a synergistic or additive effect might be expected when these agents are used in combination, as suggested by the pre-clinical studies.

Inclusion Criteria:

• Previously untreated patients with MCL aged 65 years or more, or <65 years if not eligible for intensive treatments including/not including autologous transplantation.
• MCL patients of any age who relapse/progress or are resistant after one line of chemotherapy.
• CD20+ .
• Karnofsky score of at least 70%
• Adequate renal function (Creatinine clearance >40 mL/min), with preserved diuresis.
• Adequate liver function: alanine aminotransferase (ALT)/aspartate aminotransferase (AST) <2.5 x upper limit of normal (ULN) value, total bilirubin <2 mg/dL, unless directly attributable to the patient's tumor.
• Negative serum pregnancy test 1 week prior to treatment both for pre-menopausal women and for women who are <2 years after onset of menopause.
• Hepatitis B core antibody (HBcAb) positive patients may be enrolled if correct antiviral prophylaxis is administered at least 2 weeks before initiating protocol treatment.
• Written informed consent.

Exclusion Criteria:

• Prior treatment with Bendamustine.
• Refractoriness to Rituximab, defined as progressive disease during a previous cycle including this drug, or relapse within 6 months to any previous cycle including Rituximab.
• Previous Rituximab infusion-related severe reactions.
• Human immunodeficiency virus (HIV) positive.
• Medical conditions or organ injuries that could interfere with administration of therapy.
• Active bacterial, viral, or fungal infection requiring systemic therapy.
• Seizure disorders requiring anticonvulsant therapy.
• Severe chronic obstructive pulmonary disease with hypoxaemia.
• History of severe cardiac disease: New York Heart Association (NYHA) functional class III-IV, myocardial infarction within 6 months, ventricular tachyarrhythmias, dilatative cardiomyopathy, or unstable angina.
• Uncontrolled diabetes mellitus.
• Active secondary malignancy.
• Known hypersensitivity or anaphylactic reactions to murine antibodies and proteins (for patients treated with Rituximab), to Bendamustine or mannitol.
• Fertile men and women of childbearing potential unless surgically sterile or using adequate measures of contraception.
• Major surgery within 4 weeks of study Day 1.
• HBsAg+ and HCV+ patients
• Any co-existing medical or psychological condition that would preclude participation in the study or compromise the patient's ability to give informed consent, or that may affect the interpretation of the results, or render the patient at high risk from treatment complications.