Inclusion Criteria:

• Adult patients who are at least 18 years old
• Histologically confirmed low grade or intermediate-grade B-cell lymphoma
• Relapsed or refractory to at least one standard chemotherapy regimen. Patients who have received Rituximab alone without having received a cytotoxic agent are not eligible.
• Measurable disease, defined by the Cheson lymphoma criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Life expectancy greater than 12 weeks

• Laboratory values obtained ≤2 weeks prior to entry

  • Absolute neutrophil count (ANC) ≥ 1000 x 10 9/L
  • White blood cell (WBC) count > 2.5 x 10 9/L
  • Platelets ≥ 75 x 10 9/L
  • Hemoglobin (Hg) > 9.0 g/dL
  • Total bilirubin ≤2.0 mg/dL
  • Aspartate transaminase (AST)/alanine transaminase (ALT) ≤3 × upper limit of normal (ULN)
  • Serum creatinine ≤2.0 mg/dL
• Normal cardiac function, defined as an ejection fraction ≥45% determined by pretreatment radionuclide ventriculography (RVG) or echocardiogram.
• Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent.
• Female patients of childbearing potential must have a negative serum pregnancy test within 2 weeks prior to enrollment.
• Male and female patients must use an effective contraceptive method during the study and for a minimum of 6 months after study treatment.

Exclusion Criteria:

• Previously untreated B-cell lymphoma.
• Received previous treatment with clofarabine.
• Patients with known AIDS-related or HIV-positive lymphoma.
• Autologous bone marrow or stem cell transplant within 6 months of study entry.
• Prior radiotherapy to the only site of measurable disease.
• Any medical condition that requires chronic use of oral high-dose corticosteroids greater than 20 mg/day prednisone.
• Active autoimmune thrombocytopenia.
• Use of investigational agents within 30 days or any anticancer therapy within 3 weeks before study entry. The patient must have recovered from all acute toxicities from any previous therapy.
• Patients with an active, uncontrolled systemic infection considered to be opportunistic, life threatening, or clinically significant at the time of treatment or with a known or suspected fungal infection (ie, patients on parenteral antifungal therapy).
• Active secondary malignancy.
• Pregnant or lactating patients.
• Any significant concurrent disease, illness, or psychiatric disorder that would compromise patient safety or compliance, interfere with consent, study participation, follow up, or interpretation of study results.
• Patients with active or untreated central nervous system (CNS) lymphoma.