| Exclusion Criteria: | 1) Prior use of any monoclonal antibody (other than anti-CD20; see exception below) within 3 months of the start of Cycle 1 : Prior treatment with GA101.
2) Chemotherapy or other investigational therapy within 28 days prior to the start of Cycle 1
3) Radiation therapy within 42 days prior to the start of Cycle 1
4) Prior treatment with bendamustine within 2 years of the start of Cycle 1 Patients with prior bendamustine treatment (i.e., > 2 years prior to the start of Cycle 1) are eligible if they meet both of the following criteria: 1. Achieved either a partial or complete response to the bendamustine regimen of at least 12 months in duration prior to relapse/progression and 2. Experienced progression following a regimen containing an alkylating agent (e.g., cyclophosphamide, vincristine, prednisolone [CVP]) or an anthracycline (e.g., CHOP or etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin [EPOCH])
5) Prior allogeneic stem-cell transplant
6) History of severe allergic or anaphylactic reactions to monoclonal antibody therapy (e.g., patients in whom re-dosing with rituximab would be contraindicated for safety reasons)
7) History of sensitivity to mannitol
8) Central nervous system lymphoma, prior diffuse large B-cell lymphoma (DLBL), or histological evidence of transformation to a high-grade or diffuse large B-cell lymphoma.
9) History of other malignancy that could affect compliance with the protocol or interpretation of results Patients with a history of curatively treated basal or squamous cell carcinoma of the skin or in situ carcinoma of the cervix are generally eligible. Patients with a malignancy that has been treated, but not with curative intent, will also be excluded, unless the malignancy has been in remission without treatment for >/= 2 years prior to enrollment.
10) Evidence of significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results, including significant cardiovascular disease (such as New York Heart Association Class III or IV cardiac disease, myocardial infarction within the last 6 months, unstable arrhythmias, or unstable angina) or pulmonary disease (including obstructive pulmonary disease and history of bronchospasm)
11) Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (excluding fungal infections of nail beds) or any major episode of infection requiring treatment with IV antibiotics or hospitalization (relating to the completion of the course of antibiotics) within 4 weeks of the start of Cycle 1
12) Vaccination with a live vaccine a minimum of 28 days prior to randomization
13) Recent major surgery (within 4 weeks prior to the start of Cycle 1), other than for diagnosis
14) Any of the following abnormal laboratory values: Creatinine > 1.5 times the upper limit of normal (unless creatinine clearance normal), or creatinine clearance < 40 mL/min; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 times the upper limit of normal; Total bilirubin >/=3 x ULN; Platelet count < 100 × 10^9/L (unless due to underlying disease, as established by extensive bone marrow involvement);. Neutrophil count < 1.5 × 10^9/L (unless due to underlying disease, as established by extensive bone-marrow involvement); Hemoglobin < 9 g/dL (unless due to underlying disease, as established by extensive bone-marrow involvement).
15) Presence of positive test results for hepatitis B surface antigen (HBsAg); antibody to hepatitis B core antigen [anti-HBc]) with detectable viral load (i.e., positive hepatitis B virus [HBV] DNA); or hepatitis C (hepatitis C virus [HCV] antibody serology testing)
16) Patients with chronic hepatitis B or seropositive occult (HBV) infection will be excluded. Patients with seronegative occult HBV infection or past HBV infection (defined as anti-HBc positive and HBV DNA negative) may be eligible if they are willing to be followed according to the protocol for HBV DNA testing (limited to 20 patients). Patients positive for HCV antibody are eligible only if PCR is negative for HCV RNA.
17) Known history of Human Immunodeficiency Virus (HIV) seropositive status
18) Positive test results for Human T-Lymphotropic Virus Type 1 (HTLV 1) virus in endemic countries (endemic countries include Japan, the Caribbean basin, South America, sub-Saharan Africa, and Melanesia).
19) Women who are pregnant or lactating
20) Fertile men or women of childbearing potential unless 1) surgically sterile or using an adequate measure of contraception such as oral contraceptives, intrauterine device, or barrier method of contraception in conjunction with spermicidal jelly. Effective contraception is required while receiving GA101 or bendamustine. For women, effective contraception is required to continue for >/= 12 months after the last dose of GA101. For men, effective contraception is required to continue for >/= 3 months after the last dose of GA101. For both men and women receiving bendamustine alone, effective contraception is required to continue for >/= 3 months after the last dose of bendamustine.
21) Ongoing corticosteroid use > 30 mg/day prednisone or equivalent Patients receiving corticosteroid treatment </= 30 mg/day prednisone or equivalent must be documented to be on a stable dose 1 week prior to the baseline CT/MRI scans obtained during screening. |