Ipilimumab and Rituximab In Treating Patients With Relapsed or Refractory B-Cell Lymphoma

Inclusion Criteria:

• Previously treated, histologically confirmed CD20+ B cell lymphoma; bone marrow biopsies as the sole means of diagnosis are not acceptable, but they may be submitted in conjunction with nodal biopsies or extra nodal biopsies; fine needle aspirates are not acceptable
• All patients must be informed of the investigative nature of the clinical trial and give written informed consent in accordance with institutional and federal guidelines
• Able to adhere to the study visit schedule and other protocol requirements
• Karnofsky >= 70%
• Life expectancy expected to be greater than 3 months
• Leukocytes > 3,000/mcL
• Absolute neutrophil count > 1,000/mcL
• Platelets > 50,000/mcL
• Total bilirubin < 2.0
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 x institutional upper limit of normal
• Serum creatinine =< 1.5 x upper limit of normal or calculated creatinine clearance > 50 ml/min/1.73 M^2 by the modified Cockcroft and Gault Formula or creatinine clearance > 50 mL/min obtained from a 24-hour urine collection
• At least one measurable lesion according to International workshop lymphoma response criteria (Cheson 2007); there must be measurable lymphadenopathy to follow with serial exam and/or imaging
• All previous cancer therapy, including radiation, hormonal therapy and surgery, must have been discontinued at least 4 weeks prior to treatment in this study
• Patients must have evidence of progression of disease during or after last treatment
• Submission of original biopsy for review and verification by Participating Center hematopathologist
• Disease free of prior malignancies for >= 3 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, or carcinoma "in situ" of the cervix or breast

Exclusion Criteria:

• Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
• Patients with a history of prior treatment with ipilimumab
• Patients with a history of prior treatment with an anti-PD 1 antibody, CD137 agonist or other immune activating therapy such as anti-CD 40 antibody are excluded unless 5 half-lives of the agent (minimum of 8 weeks) have intervened since the therapy; patients who have received prior vaccine therapy are eligible
• Patients who are receiving any other investigational agents
• Autoimmune disease: patients with a history of inflammatory bowel disease, including ulcerative colitis and Crohn's disease, are excluded from this study, as are patients with a history of symptomatic disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener's Granulomatosis]); central nervous system (CNS) or motor neuropathy considered of autoimmune origin (e.g. Guillain-Barre Syndrome and Myasthenia Gravis, multiple sclerosis)
• Patients with known immune impairment who may be unable to respond to anti-cytotoxic T-lymphocyte antigen 4 (CTLA 4) antibody
• Patients with known brain metastases are excluded
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab
• Patients on systemic corticosteroids (except for patients on stable doses of hormone replacement therapy such as hydrocortisone), or other immunosuppressants (e.g., infliximab, mycophenolate mofetil) are excluded
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Patients with chronic human immunodeficiency virus (HIV), hepatitis B or hepatitis C infections are excluded
• Pregnant women are excluded from this study
• HIV-positive patients on combination antiretroviral therapy are ineligible
• Rituximab within three months