Ofatumumab and Bortezomib in Treating Patients With Previously Untreated Waldenstrom Macroglobulinemia
Condition: Waldenström Macroglobulinemia
MeSH terms: Waldenstrom Macroglobulinemia
Intervention: ofatumumab; bortezomib; laboratory biomarker analysis
Intervention description: Given IV; Given SC; Correlative studies
Intervention MeSH terms: Bortezomib; Ofatumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 3.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well giving ofatumumab together with bortezomib works in
      treating patients with previously untreated Waldenstrom macroglobulinemia. Monoclonal
      antibodies, such as ofatumumab and bortezomib, can block cancer growth in different ways.
      Some block the ability of cancer cells to grow and spread. Others find cancer cells and help
      kill them or carry cancer-killing substances to them. Giving ofatumumab together with
      bortezomib may be a better way to block cancer growth
    

Eligibility criteria:

        Inclusion Criteria:

          -  Diagnosis of Waldenstrom Macroglobulinemia and presence of cluster of differentiation
             (CD)20+ tumor cells as determined by immune-histochemistry or flow cytometric analysis
             in bone marrow or representative lymphoid tissue specimen; to be deemed eligible,
             patients must meet at least one of the following criteria:

               -  Rising immunoglobulin (Ig)M

               -  Hemoglobin =< 10 g/dL

               -  Platelet count =< 100 x 10^9/L

               -  Symptomatic or bulky lymphadenopathy or organomegaly

               -  Systemic manifestations of Waldenstrom Macroglobulinemia (WM), such as
                  hyperviscosity symptoms (patients with symptoms of hyperviscosity syndrome must
                  be treated with plasmapheresis to control the syndrome prior to enrollment),
                  neuropathy, amyloidosis, cryoglobulinemia, B-symptoms, or recurrent bleeding

          -  Must have a measurable disease as defined by the monoclonal IgM level of 1 g/dL on
             serum protein electrophoresis (SPEP); if the level of IgM on SPEP is less than 1 g/dL
             in patients who meet any criteria in inclusion criteria 2, then the IgM level obtained
             from nephelometric measurement may be used to justify this criterion

          -  Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =< 2

          -  Have a life expectancy of >= 3 months

          -  Absolute neutrophil count >= 1.0 x 10^9/L unless the result of disease infiltration of
             bone marrow

          -  Platelet count >= 50 x 10^9/L unless the result of disease infiltration of bone marrow

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 3 x the
             institutional upper limit of normal (ULN)

          -  Total bilirubin =< 3 mg/dL or 1.5 x institutional ULN, whichever is lower

          -  Serum creatinine =< 3 mg/dL

          -  Female patients are either post-menopausal or surgically sterilized otherwise they
             must agree to use acceptable contraceptive methods (e.g. double barrier) during
             treatment

          -  Male subjects, even if surgically sterilized (i.e., status post vasectomy) must agree
             to one of the following:

               -  Practice effective barrier contraception during the entire study treatment period
                  and through a minimum of 30 days after the last dose of study drug

               -  Completely abstain from heterosexual intercourse

          -  Patient or legal representative must understand the investigational nature of this
             study and sign an Independent Ethics Committee/Institutional Review Board approved
             written informed consent prior to receiving any study related procedure

        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