Ofatumumab and Bendamustine Hydrochloride With or Without Bortezomib in Treating Patients With Untreated Follicular Non-Hodgkin Lymphoma
Condition: Ann Arbor Stage III Grade 1 Follicular Lymphoma; Ann Arbor Stage III Grade 2 Follicular Lymphoma; Ann Arbor Stage III Grade 3 Follicular Lymphoma; Ann Arbor Stage IV Grade 1 Follicular Lymphoma; Ann Arbor Stage IV Grade 2 Follicular Lymphoma; Ann Arbor Stage IV Grade 3 Follicular Lymphoma; Grade 3a Follicular Lymphoma
MeSH terms: Lymphoma; Lymphoma, Follicular
Intervention: Bendamustine Hydrochloride; Bortezomib; Fludeoxyglucose F-18; Laboratory Biomarker Analysis; Ofatumumab; Positron Emission Tomography with Radiolabeled Targeting Agent
Intervention description: Given IV; Given IV or SC; Undergo FDG-PET; Correlative studies; Given IV; Undergo FDG-PET
Intervention MeSH terms: Deoxyglucose; Bortezomib; Bendamustine Hydrochloride; Ofatumumab; Fluorodeoxyglucose F18; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 135.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This randomized phase II trial studies how well ofatumumab and bendamustine hydrochloride
      with or without bortezomib works in treating patients with untreated follicular non-Hodgkin
      lymphoma. Monoclonal antibodies, such as ofatumumab, may block cancer growth in different
      ways by targeting certain cells. Drugs used in chemotherapy, such as bendamustine
      hydrochloride, work in different ways to stop the growth of cancer cells, either by killing
      the cells, by stopping them from dividing, or by stopping them from spreading. Bortezomib may
      stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
      Bortezomib may also stop the growth of cancer cells by blocking blood flow to the tumor. It
      is not yet known whether ofatumumab and bendamustine hydrochloride are more effective with
      bortezomib in treating patients with follicular non-Hodgkin lymphoma.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Histologically confirmed follicular non-Hodgkin lymphoma, World Health Organization
             (WHO) classification grade 1, 2, or 3a (> 15 centroblasts per high-power field with
             centrocytes present)

               -  Bone marrow biopsies as the sole means of diagnosis are not acceptable, but they
                  may be submitted in conjunction with nodal biopsies

               -  Fine-needle aspirates are not acceptable

               -  Failure to submit pathology within 60 days of patient registration will be
                  considered a major protocol violation

          -  Patients must have at least one of the following indicators of poor risk disease:

               -  >= 3 risk factors by the Follicular Lymphoma International Prognostic Index, or 2
                  risk factors by the Follicular Lymphoma International Prognostic Index and at
                  least one bulky mass or lymph node > 6 cm in size

               -  Follicular Lymphoma International Prognostic Index (FLIPI score):

                    -  Age > 60 years

                    -  Involvement of > 4 nodal sites

                    -  Stage III-IV disease

                    -  Hemoglobin < 12.0 g/dL

                    -  Lactate dehydrogenase (LDH) > upper limit of normal (ULN)

                         -  0-1 of the above risk factors: low risk

                         -  2 risk factors: intermediate risk

                         -  >= 3 risk factors: poor risk

          -  No prior cytotoxic chemotherapy, radiotherapy, immunotherapy, or radioimmunotherapy

          -  No corticosteroids are permitted, except for maintenance therapy for a non-malignant
             disease or to prevent treatment-related ofatumumab reactions (maintenance therapy dose
             must not exceed 20 mg/day prednisone or equivalent)

          -  Measurable disease must be present either on physical examination or imaging studies;
             non-measurable disease alone is not acceptable; any tumor mass > 1 cm is acceptable;
             lesions that are considered non-measurable include the following:

               -  Bone lesions

               -  Leptomeningeal disease

               -  Ascites

               -  Pleural/pericardial effusion

               -  Inflammatory breast disease

               -  Lymphangitis cutis/pulmonis

               -  Bone marrow involvement (involvement by non-Hodgkin lymphoma should be noted)

          -  Patients must have no known central nervous system (CNS) involvement by lymphoma

          -  Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-2

          -  Patients must be non-pregnant and non-nursing; pregnant or nursing patients may not be
             enrolled; women of childbearing potential must have a negative serum or urine
             pregnancy test within 14 days prior to registration; in addition, women and men of
             childbearing potential must commit to use an effective form of contraception
             throughout their participation in this study; appropriate methods of birth control
             include abstinence, oral contraceptives, implantable hormonal contraceptives
             (Norplant), or double barrier method (diaphragm plus condom)

          -  Patients with human immunodeficiency virus (HIV) infection are eligible; patients with
             HIV infection must meet the following: no evidence of co-infection with hepatitis B or
             C; CD4+ count > 400/ul; no evidence of resistant strains of HIV; on anti-HIV therapy
             with an HIV viral load < 50 copies HIV RNA/mL; no history of acquired immunodeficiency
             syndrome (AIDS)-defining conditions; no zidovudine or stavudine are allowed owing to
             overlapping toxicity with chemotherapy

          -  Patients must have no evidence of active hepatitis B or C infection (i.e., no positive
             serology for anti-hepatitis B core [HBc] or anti-hepatitis C virus [HCV] antibodies);
             hepatitis B virus (HBV) seropositive patients (hepatitis B surface antigen [HBsAg] +)
             are eligible if HBV deoxyribonucleic acid (DNA) is undetectable at baseline and they
             are closely monitored for evidence of active HBV infection by HBV DNA testing at each
             treatment cycle; after completing treatment, HBsAg + patients must be monitored by HBV
             DNA testing every 2 months for 6 months post-treatment, while continuing lamivudine

          -  Granulocytes >= 1,000/uL

          -  Platelet count >= 75,000/uL

          -  Creatinine =< 2.0 mg/dL

          -  Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x upper
             limits of normal (ULN)

          -  Bilirubin =< 2 x ULN