Ofatumumab and Bortezomib in Subjects With Relapsed CD20+Diffuse Large B Cell, Follicular, or Mantle Cell Lymphoma
Condition: Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Recurrence
Intervention: Ofatumumab; Bortezomib
Intervention description: Given intravenously; Given intravenously
Intervention MeSH terms: Bortezomib; Ofatumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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 relapsed diffuse large B cell lymphoma (DLBCL), follicular lymphoma
      (FL), or mantle cell lymphoma (MCL). Monoclonal antibodies, such as ofatumumab, 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.
      Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for
      cell growth. Giving ofatumumab together with bortezomib may help kill more cancer cells
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients must have biopsy sample obtained within 6 months of study entry that:

          -  Is histologically confirmed DLBCL, MCL or FL, by an Oregon Health and Science
             University (OHSU) hematopathologist

          -  Retains expression of CD20+

          -  Patients must be refractory to or have recurrent disease after prior rituximab
             containing treatment; relapse or progression is defined according the International
             Working Group (IWG) response criteria

          -  FL patients must have disease-related symptoms, cytopenias, threatened end-organ
             function, bulky or progressive disease, or it is the patient's preference to be
             treated

          -  DLBCL and MCL patients must be either transplant ineligible or have refused high dose
             therapy

          -  Patients must have radiographically measurable disease, as defined by the IWG
             criteria; the same method of assessment used to measure each lesion at baseline must
             be used for all subsequent tumor measurements throughout the study

          -  There is no limit to the number of prior treatments

          -  Eastern Cooperative Oncology Group (ECOG) performance status =< 2

          -  Absolute neutrophil count >= 1.0 K/mm^3

          -  Platelets >= 50 K /mm^3

          -  Total bilirubin =< 1.5 x normal institutional limits, unless secondary to Gilbert's
             disease

          -  Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase
             (SGOT))/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase (SGPT))
             =< 2.5 x institutional upper limit of normal (ULN)

          -  Alkaline Phosphatase < 2.5 times ULN (unless due to disease involvement of the liver
             or bone marrow)

          -  Patients must be able to comply with study procedures and follow-up examinations

          -  Women of childbearing potential (not surgically sterile or < 12 months naturally
             post-menopausal) must be willing to use medically accepted method of contraception for
             the duration and 6 months following the end of the treatment; acceptable methods of
             contraception include abstinence, barrier method with spermicidal or hormonal
             contraceptive (oral, transdermal, implanted and injected) in conjunction with a
             barrier method

          -  Men who are not surgically sterile must practice abstinence or use a barrier method of
             birth control for the duration and 6 months following the end of treatment

          -  Patients must have the ability to understand and the willingness to sign a written
             informed consent document

        Exclusion Criteria:

          -  Subjects who have current active hepatic or biliary disease (with the exception of
             patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable
             chronic liver disease per investigator assessment)

          -  Patients who have had chemotherapy, antibody or radiotherapy within 4 weeks (6 weeks
             for nitrosoureas or mitomycin C); corticosteroids for symptom control are allowed up
             to 7 days of starting protocol treatment

          -  Patients may not have received any other investigational agents within 4 weeks, or may
             not be currently participating in any other interventional clinical study

          -  Prior treatment with ofatumumab or bortezomib

          -  Prior treatment with anti-CD20 monoclonal antibody or alemtuzumab within 3 months
             prior to start of therapy

          -  Diagnosis of another malignancy, unless the patient has been disease-free or at least
             5 years following the completion of curative intent therapy with the following
             exceptions: patients with treated non-melanoma skin cancer, in situ carcinoma, or
             cervical intraepithelial neoplasia, regardless of the disease-free duration, are
             eligible for this study if definitive treatment for the condition has been completed;
             patients with organ-confined prostate cancer with no evidence of recurrent or
             progressive disease based on prostate-specific antigen (PSA) values are also eligible
             for this study if hormonal therapy has been initiated or a radical prostatectomy has
             been performed

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to ofatumumab or bortezomib

          -  Peripheral neuropathy or neuropathic pain of Grade 2 or greater

          -  Chronic or current infectious disease requiring systemic antibiotics, antifungal, or
             anti-viral treatment such as, but not limited to, chronic renal infection, chronic
             chest infection with bronchiectasis and tuberculosis

          -  History of significant cerebrovascular disease in the past 6 months or ongoing event
             with active symptoms or sequelae

          -  Clinically significant cardiac disease including unstable angina, acute myocardial
             infarction within six months prior to randomization, congestive heart failure (New
             York Heart Association (NYHA) III-IV), and arrhythmia unless controlled by therapy,
             with the exception of extra systoles or minor conduction abnormalities

          -  Significant concurrent, uncontrolled medical condition including, but not limited to,
             renal, hepatic, gastrointestinal, endocrine, pulmonary, neurological, cerebral or
             psychiatric disease which in the opinion of the investigator may represent a risk for
             the patient

          -  Pregnant or breast feeding women

          -  Known human immunodeficiency virus (HIV) infection

          -  Positive serology for Hepatitis B (HB) defined as a positive test for HB surface
             antigen (HBsAg); in addition, if negative for HBsAG but HB core antibody (HBcAb)
             positive (regardless of HBsAb status), a HB deoxyribonucleic acid (DNA) test will be
             performed; if positive the subject will be excluded

          -  Active hepatitis C infection (HC) defined as a positive test for hepatitis C antibody
             (HCAb), in which case the investigator should reflexively perform a HC Recombinant
             Immunoblot assay (RIBA) on the same sample to confirm the result

          -  Known lymphoma involvement of the central nervous system (CNS)