A Phase I Study of Ipilimumab in Combination With Rituximab in Patients With Relapsed/Refractory CD20+ 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 times institutional upper limit of normal

- 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 =< 2.0 x upper limit of normal or calculated creatinine clearance >=
30 ml/min/1.73 M^2 by the modified Cockcroft and Gault Formula or creatinine
clearance >= 30 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