A Phase 2 Clinical Trial of Rituxan and B-Glucan PGG in Relapsed Indolent Non-Hodgkin Lymphoma

Inclusion Criteria: * Participants must meet the following criteria on screening examination to be eligible to participate in the study: * Patients must have histologically determined indolent NHL that is relapsed or primary refractory after initial therapy. Indolent NHL includes the morphologic and clinical variants: * Follicular lymphoma, grades 1-3a * Marginal zone lymphoma (extranodal, nodal, or splenic) * All nodal marginal zone lymphomas are eligible * Extranodal marginal zone lymphomas of the stomach (gastric MALT lymphomas) may not be candidates for cure with antibiotics or local radiotherapy. Patients who have failed antibiotics or local therapy are eligible for the protocol as long as they have measurable disease and are naïve to chemotherapy and monoclonal antibody therapy. * Splenic marginal zone lymphoma patients may have received prior splenectomy as long as they have measurable disease and are naïve to chemotherapy and monoclonal antibody therapy. * Re-biopsy is not mandated at relapse unless there is clinical suspicion about an alternate diagnosis. * Between 1-3 prior lines of chemoimmunotherapy and/or monotherapy with rituximab. Patients may not have had prior autologous or allogeneic stem cell transplantation. * Measurable disease that has not been previously irradiated on CT scans of at least 2 cm, OR if the patient has had previous radiation to the marker lesion(s), there must be evidence of progression since the radiation. Imaging must be completed no greater than 4 weeks prior to study enrollment. * ECOG performance status 0-2 (Appendix B, Section 17.2) * Absolute neutrophil count ≥1000 prior to treatment * Oxygen saturation ≥ 90%, no more than 2 LPM oxygen * Serum creatinine ≤ 1.5 X ULN * AST ≤ 3 X ULN * Total bilirubin ≤ 1.5 X ULN (unless there is lymphoma in the liver) * Age ≥18 years * Ability to understand and the willingness to sign a written informed consent document. Exclusion Criteria: * Participants who exhibit any of the following conditions at screening will not be eligible for admission into the study. * Patients currently receiving anticancer therapies or who have received anticancer therapies within 30 days of the start of study drug (including chemotherapy, radiation therapy, antibody based therapy, etc.). Steroids for symptom palliation are allowed, but must be either discontinued or on stable doses at the time of initiation of protocol therapy. * Patients may not be receiving any other investigational agents, or have received investigational agents within 4 weeks of beginning treatment. * Patients who have previously received PGG-Betafectin (Betafectin®) or Imprime PGG. * Patients, who have had a major surgery or significant traumatic injury within 4 weeks of start of study drug, patients who have not recovered from the side effects of any major surgery (defined as requiring general anesthesia) or patients that may require major surgery during the course of the study. * Patients with known leptomeningeal or brain metastases. Imaging or spinal fluid analysis to exclude CNS involvement is not required, unless there is clinical suspicion by the treating investigator. * History of severe allergic or anaphylactic reactions to monoclonal antibody therapy or a known hypersensitivity to baker's yeast. * Patients with known HIV infection or hepatitis B or C infection.HIV testing is not mandated and is to be performed at the discretion of the treating investigator. * Patients with a systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). * Prior history of another malignancy (except for non-melanoma skin cancer or in situ cervical or breast cancer) unless disease free for at least three years. Patients with prostate cancer are allowed if PSA is less than 1. * Patients should not receive immunization with attenuated live vaccine within one week of study entry or during study period. * Female patients who are pregnant or breast feeding, or adults of reproductive potential who are not using effective birth control methods. Women of child bearing potential (WOCBP) or male study participants of reproductive potential must agree to use double barrier birth control method of contraception during the course of the study treatment period and for 3 months after completing study treatment. \-- WOCBP are defined as sexually mature women who have not undergone a hysterectomy or who are not postmenopausal (no menses) for at least 12 consecutive months. WOCBP must have a negative urine or serum pregnancy test within 7 days prior to administration of treatment. * History of noncompliance to medical regimens. * Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study such as: * New York Heart Association Class III or IV cardiac disease, including pre-existing clinically significant arrhythmia, congestive heart failure, or cardiomyopathy * unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease * Other uncontrolled intercurrent illness that would limit adherence to study requirements.