Evaluation of the Safety and Efficacy of Nipent, Cytoxan, and Rituxan

Inclusion Criteria

• Histologically or cytologically proven, stage III or IV, low-grade B-cell NHL, as defined by the updated WHO modification of the REAL classification for peripheral B-cell neoplasms: B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma; Lymphoplasmacytic lymphoma/immunocytoma; Follicular lymphoma; Extranodal marginal zone B-cell lymphoma of MALT type; Nodal marginal zone B-cell lymphoma (+/- monocytoid B-cells); Lymphoma with primarily bone marrow-only disease are considered eligible
• Bulky lymphoma or Stage II disease requiring chemotherapy will be considered for enrollment with documented Sponsor Investigator approval prior to registration.
• CT or MRI scans confirming measurable tumor size (lymph node must be >1cm in its longest transverse diameter). Measurement by physical exam is acceptable in the case of palpable and reproducibly measurable axillary or other superficial tumors.
• Positive expression of cluster of differentiation antigen 20 (CD20) by biopsy or circulating lymphocytes.
• Zero or one prior chemotherapeutic or immunotherapeutic treatment regimen for B-cell NHL.
• Male or female greater than or equal to 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2.
• Adequate renal function: Creatinine less than 1.5 mg/dL; blood urea nitrogen (BUN) less than 30 mg/dL or a creatinine clearance greater than or equal to 60 mL/min based on calculation of creatinine clearance using the Cockcroft-Gault method or from a 24-hour urine collection. Creatinine clearance 40- 59 mL/min from a 24-hour urine collection would require a Nipent dose reduction of 25%. Patients with a Creatinine clearance <40 mL/min from a 24-hour urine collection will be excluded.
• Adequate bone marrow function: absolute neutrophil count (ANC) greater than or equal to 1,000 cells/µL; Platelet count greater than or equal to 75,000 cells/µL; Hemoglobin greater than or equal to 9 g/dL. Patients with idiopathic thrombocytopenia or autoimmune hemolytic anemia are eligible with prior approval of Sponsor Investigator.
• Adequate liver function: Bilirubin less than or equal to 2.0 mg/dL; AST and ALT less than or equal to 5 times upper limit of normal (ULN).
• Adequate cardiac function in the judgment of the Investigator, including New York Heart Association (NYHA) classification of I or II.
• Female patients of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration.
• Patient agrees to use an acceptable method of birth control, if fertile patient (male or female), to avoid pregnancy for the duration of the study and for at least 3 months thereafter.
• Completed Patient Informed Consent Form.

Exclusion Criteria

• Previous or current intermediate or high-grade lymphoma.
• White blood cell count (WBC) greater than 30,000 cells/µL.
• Received prior therapy using Rituxan, unless such therapy was completed at least 6 months prior to study registration. Patients whose disease was non-responsive to prior Rituxan therapy will be excluded.
• Known sensitivity to Nipent, Rituxan, Cytoxan or any component of these drugs.
• Patient received replacement steroid therapy less than 4 weeks prior to study registration.
• History of other malignancy that could affect the diagnosis or assessment of the study treatment.
• Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) illness.
• Known prior history of and/or active viral hepatitis (HBV or HCV).
• Patient is unable to comply with the requirements of this study.
• Patients with Richter's transformation will be excluded.