A Randomized Phase II Trial of Ofatumumab and Bendamustine vs. Ofatumumab, Bortezomib (NSC # 681239, IND # 58443) and Bendamustine in Patients With Untreated Follicular Lymphoma

Inclusion Criteria:

- Histologically confirmed follicular non-Hodgkin lymphoma, 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

- Patients must have at least one of the following indicators of poor risk disease:

- >= 3 risk factors by the Follicular Lymphoma International Prognostic Index
(FLIPI score), or 2 risk factors by the FLIPI and at least one bulky mass or
lymph node > 6 cm in size;

- FLIPI score:

- Age > 60 years

- Involvement of > 4 nodal sites

- Stage III-IV disease

- Hemoglobin < 12.0 mg/dL

- 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; due to the unknown teratogenic
potential of this regimen, pregnant or nursing patients may not be enrolled; women of
childbearing potential must have a negative serum or urine pregnancy test 10-14 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 due to the teratogenic potential of the therapy utilized in this trial;
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/µl; no evidence of resistant strains of HIV; on
anti-HIV therapy with an HIV viral load < 50 copies HIV ribonucleic acid (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/μL

- Platelet count >= 75,000/μL

- Creatinine =< 2.0 mg/dL

- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN

- Bilirubin =< 2 x ULN