Study to Assess the Effect of Treatment With Bendamustine in Combination With Rituximab on QT Interval in Patients With Advanced Indolent Non-Hodgkin’s Lymphoma (NHL) or Mantle Cell Lymphoma (MCL)

Key Inclusion Criteria:

Histopathologic confirmation of one of the following CD20+ B-cell non-Hodgkin's lymphomas. Tissue diagnostic procedures must be performed within 6 months of study entry and with biopsy material available for review:

follicular lymphoma (grade 1 or 2)
immunoplasmacytoma/immunocytoma (Waldenstrom's macroglobulinemia)
splenic marginal zone B-cell lymphoma
extra-nodal marginal zone lymphoma of mucosa associated lymphoid tumor (MALT) type
nodal marginal zone B-cell lymphoma
mantle cell lymphoma

Meets one of the following need-for-treatment criteria (with the exception of mantle cell lymphoma for which treatment is indicated):

presence of at least one of the following B-symptoms:

fever (>38ºC) of unclear etiology
night sweats
weight loss of greater than 10% within the prior 6 months
large tumor mass (bulky disease)
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
CD20-positive B cells in lymph node biopsy or other lymphoma pathology specimen
No prior treatment. Patients on "watch and wait" may enter the study if a recent biopsy (obtained within the last 6 months) is available.

Adequate hematologic function (unless abnormalities related to lymphoma infiltration of the bone marrow or hypersplenism due to lymphoma) as follows:

hemoglobin of >= 10.0 g/dL
absolute neutrophil count (ANC) >=1.5*10^9/L
platelet count >=100*10^9/L
Bidimensionally measurable disease (field not previously radiated)
Able to provide written informed consent
Eastern Cooperative Oncology Group (ECOG) performance status <=2
Estimated life expectancy >=6 months
Serum creatinine of <=2.0 mg/dL or creatinine clearance >=50 mL/min
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5* upper limit of normal (ULN), and alkaline phosphatase and total bilirubin within normal limits
Left ventricular ejection fraction (LVEF) >=50% by multiple gated acquisition scan (MUGA) or cardiac echocardiogram (ECHO), prior for any patient to be treated with rituximab/cyclophosphamide/doxorubicin/vincristine/prednisolone (R-CHOP)
A medically accepted method of contraception to be used by women of childbearing potential (not surgically sterile or at least 12 months naturally postmenopausal)
Men capable of producing offspring and not surgically sterile must practice abstinence or use a barrier method of birth control

Key Exclusion Criteria:

Chronic lymphocytic leukemia, small lymphocytic lymphoma (SLL), or grade 3 follicular lymphoma
Transformed disease. Bone marrow blasts are permitted, however, transformed disease indicating leukemic involvement is not permitted
Central nervous system (CNS) lymphomatous involvement or leptomeningeal lymphoma
Prior radiation for non-Hodgkin's lymphoma (NHL), except for a single course of locally delimited radiation therapy with a radiation field not exceeding 2 adjacent lymph node regions
Active malignancy, other than NHL, within the past 3 years except for localized prostate cancer treated with hormone therapy, cervical carcinoma in situ, breast cancer in situ, or non-melanoma skin cancer following definitive treatment
New York Heart Association (NYHA) Class III or IV heart failure, arrhythmias or unstable angina, electrocardiographic evidence of active ischemia or active conduction system abnormalities, or myocardial infarction within the last 6 months. (Prior to study entry, ECG abnormalities at screening must be documented by the investigator as not medically relevant)
Known human immunodeficiency virus (HIV) positivity
Active hepatitis B or hepatitis C infection (Hepatitis B surface antigen testing required)
Women who are pregnant or lactating
Corticosteroids for treatment of lymphoma within 28 days of study entry. Chronically administered low-dose corticosteroids (e.g., prednisone ≤20 mg/day) for indications other than lymphoma or lymphoma-related complications are permitted
Any serious uncontrolled, medical or psychological disorder that would impair the ability of the patient to receive therapy
Any condition which places the patient at unacceptable risk or confounds the ability of the investigators to interpret study data
Any other investigational agent within 28 days of study entry
Known hypersensitivity to bendamustine, mannitol, or other study-related drugs
The patient has Ann Arbor stage I disease
The patient has a history of congenital long QT syndrome
The patient has a history of cardiac disease with significant potential for QT prolongation
The patient has screening electrocardiography (ECG) on Day 1 of Cycle 1 with QTcF interval >450 ms that is confirmed by a second ECG. If the QTcF interval is >450 ms on both ECGs, the ECGs will be sent to eResearch Technology, Inc. (ERT), the Central ECG Reader vendor, for an overread (with 24-hour turn around time) and ERT will make a final decision on enrollment
The patient has serum potassium or magnesium less than the lower limit of normal