A Study of TRU-016 in Combination With Rituximab and Bendamustine in Subjects With Relapsed Indolent Lymphoma

Inclusion Criteria

Age 18 years or older
Histologically confirmed diagnosis of indolent non-Hodgkin's B-cell lymphoma (ie, follicular lymphoma, small lymphocytic lymphoma, and marginal zone lymphoma) that has relapsed (relapsed is defined as confirmed progressive disease (PD) after receiving the most recent prior therapy, or failure to achieve at least a partial response (PR) while receiving the most recent prior therapy)
At least one prior line of therapy for indolent lymphoma
Bi-dimensionally measurable disease with at least one lesion measuring >=1.5 cm in a single dimension
Eastern Cooperative Oncology Group (ECOG) performance status of <= 2
Creatinine clearance of >40 mL/min as calculated by the

Cockcroft-Gault method as follows:

(140 - age) * (weight in kg [* 0.85 if female] / 72 * serum creatinine level) 7. Adequate hepatic function, indicated as follows:

aspartate aminotransferase (AST) of <2.5 x upper limit of normal (ULN)
alanine aminotransferase (ALT) of <2.5 x ULN
total bilirubin of <= 1.5 x ULN 8. Absolute neutrophil count (ANC) >=1000/mm3 (1000/µL) 9. Platelet count >= 100,000/mm3 10. Female subjects of child-bearing potential and male subjects must use an acceptable form of birth control for the duration of their study participation and for 6 months after completing study drug dosing; acceptable forms of birth control, unless dictated otherwise by local regulatory authorities 11. For women of childbearing potential, a negative serum pregnancy test result obtained during the screening period and a negative urine pregnancy test result within 24 hours before first administration of study drug 12. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information

Exclusion Criteria

Diagnosis of grade 3b follicular lymphoma or transformed lymphoma of any grade
Previously received TRU-016
Prior treatment with rituximab if subject discontinued rituximab due to unresolved toxicity

Refractory to bendamustine, defined as follows:

progression within 6 months of last dose of bendamustine
failed to achieve at least a PR while receiving bendamustine
discontinued bendamustine due to toxicity
received bendamustine within 6 months prior to first dose of study drug
Received chemotherapy, radiotherapy, or immunotherapy including investigational agents within 28 days prior to the first dose of study drug
Received therapeutic corticosteroids at doses equivalent to >10 mg prednisone per day for longer than 5 days within 14 days prior to the first dose of study drug, except if needed as a pre-medication
Received filgrastim or equivalent within 14 days prior to screening (ie, collection of samples for laboratory tests) or pegfilgrastim within 28 days prior to screening (ie, collection of samples for laboratory tests)
Prior allogeneic bone marrow transplant
Prior autologous bone marrow transplant within 12 months prior to the first dose of study drug
Received blood or platelet infusion within 7 days prior to screening (ie, collection of samples for laboratory tests)
Previous or concurrent additional malignancy except non-invasive, non-melanomatous skin cancer or in situ carcinoma of the cervix, or other solid tumors if the subject has been disease-free for a minimum of 2 years prior to the first dose of study drug
Known central nervous system or leptomeningeal lymphoma

Any significant concurrent medical diseases or conditions, including but not limited to the following:

Clinically significant pulmonary dysfunction requiring oxygen therapy
An active infection (viral, bacterial, or fungal) requiring systemic therapy; subjects receiving prophylactic therapy are eligible
Known allergy to mannitol
History of positive serology for human immunodeficiency virus (HIV)
Positive serology for hepatitis B (surface antigen or core antibody) Note: If a positive test result for hepatitis B core antibody is due to immunoglobulin treatment, the subject may be enrolled if the hepatitis B viral deoxyribonucleic acid (DNA) is negative.
Positive serology for hepatitis C
Pregnant or breastfeeding
Other severe, acute, or chronic medical or psychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration or may interfere with safety
Any condition that, in the investigator's opinion, makes the subject unsuitable for study participation