Trial of Bendamustine, Bortezomib, and Rituximab in Patients With Previously Untreated Low Grade Lymphoma

Inclusion Criteria

• •1. Histologically-confirmed indolent lymphoma by the World Health Organization (WHO) classification. The biopsy must fulfill one of the following criteria:
• •* Follicular lymphoma, grade 1 or 2
• •* Marginal zone lymphoma
• •* Small lymphocytic lymphoma (circulating lymphocyte count must be \<5,000)
• •* Lymphoplasmacytic lymphoma
• •2. At least one of the following criteria must be met:
• •* Presence of any symptoms related to lymphoma. These can include classic B-symptoms (fever \[\>38°C\] of unclear etiology, night sweats, weight loss of greater than 10% within the prior 6 months) or other lymphoma-related symptoms (fatigue, pain, etc.).
• •* Large tumor mass (bulky disease) characterized by lymphomas with a diameter of more than 3 cm in three or more regions or by a lymphoma with a diameter \>7 cm in one region
• •* Presence of lymphoma-related complications, including narrowing of ureters or bile ducts, tumor-related compression of a vital organ, lymphoma-induced pain, cytopenias related to lymphoma/leukemia, splenomegaly, pleural effusions, or ascites
• •* Hyperviscosity syndrome due to monoclonal gammopathy
• •3. The lymph node biopsy or other lymphoma pathology specimen has CD20+ B-cells.
• •4. Ann-Arbor Stage 2 (non-contiguous), 3, or 4 disease.
• •5. No previous systemic treatment for lymphoma. Patients may have had a single course of radiation therapy to a limited field (i.e., not exceeding two adjacent lymph node regions).
• •6. The patient has bidimensionally measurable disease with at least 1 lesion measuring ≥2.0 cm in a single dimension, and the field was not previously radiated.
• •7. An Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2.
• •8. Adequate hematologic function ≤7 days prior to start of study treatment:
• •* Hemoglobin ≥10.0 g/dl
• •* Absolute neutrophil count (ANC) ≥1000/µL
• •* Platelet count ≥75,000/µL. If low counts are attributable to bone marrow infiltration or hypersplenism due to lymphoma, ANC must be ≥750/µL and platelets ≥50,000/µL.
• •9. Calculated or measured creatinine clearance ≥30 mL/min ≤7 days of study enrollment (using Cockcroft-Gault method).
• •10. Adequate hepatic function (≤2.5 x upper limit of normal \[ULN\] for alanine aminotransferase \[ALT\], aspartate aminotransferase \[AST\], and alkaline phosphatase and total bilirubin within normal limits).
• •11. Patients must be ≥18 years of age.
• •12. Women of childbearing potential must agree to use a medically acceptable method of birth control (e.g., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for 12 months after their last dose of rituximab. Men must use an acceptable method/form of contraception for the duration of treatment and for 3 months after the end of treatment.
• •13. Patients must be able to understand the investigational nature of this study and give written informed consent prior to study entry.