Ofatumumab and Bortezomib in Treating Patients With Previously Untreated Waldenstrom Macroglobulinemia

Exclusion Criteria

• •Pregnant and nursing female patients
• •Prior anti-neoplastic therapy for WM; the use of plasmapheresis to manage the symptoms of hyperviscosity and other IgM paraprotein mediated symptoms is allowed and does not disqualify a patient from the study; if a patient undergoes plasmapheresis within 8 weeks of starting the study treatment then the IgM level prior to plasmapheresis should be used for response assessment; neoplastic use of glucocorticoids is prohibited during the screening and treatment period; patients with active hyperviscosity symptoms should not be enrolled in this study unless the symptoms resolve after plasmapheresis
• •Unwilling or unable to follow protocol requirements
• •Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug
• •Received an investigational agent within 30 days prior to enrollment
• •Known human immunodeficiency virus (HIV) positive
• •Positive serology for hepatitis B (HB) defined as a positive test for hepatitis B surface antigen (HBsAg); in addition, if HBsAg is negative and hepatitis B core antibody (HBcAb) is positive, regardless of hepatitis B surface antibody (HBsAb) status, a HB deoxyribonucleic acid test will be performed and if HB DNA is positive the patient will be excluded; if a patient is HBsAg negative, HBcAb positive, and HBsAb positive, indicating past but not active infection, the patient will be included on the study
• •Positive serology for hepatitis C (HC) defined as a positive test for Hep C by enzyme immunoassays (EIA), in which case reflexively perform a HC recombinant immunoblot assay (RIBA) on the same sample to confirm the result
• •Diagnosis of a malignant disorder other than WM within 3 years of the study enrollment with the exception of completely resected non-melanoma skin cancer and successfully treated in-situ cancer
• •Uncontrolled infection
• •Hypersensitivity to bortezomib, boron, or mannitol
• •Grade 2 or greater peripheral neuropathy; since WM is known to cause peripheral neuropathy (PN), if, in investigator's judgement, a patient has Grade 2 PN related to WM, then he/she can be enrolled onto the study; under no circumstances patient with greater than Grade 2 PN can be enrolled
• •Myocardial infarction within 6 months of enrollment; New York Heart Association (NYHA) Class III or more heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias; arrhythmias requiring active therapy other than chronic stable atrial fibrillation; if a patient has an implanted cardiac pacemaker and is otherwise well can be enrolled onto this study after demonstrating normal ejection fraction and clearance from a cardiologist; at the time of screening any electrocardiographic abnormality has to be documented as not medically relevant by the investigator before the patient proceeds to the enrollment phase
• •Any serious medical or psychiatric illness that may interfere with participation in the study
• •Patients with symptoms of hyperviscosity syndrome will not be enrolled on the study until they undergo plasmapheresis that results in resolution of symptoms and optimal control of the syndrome