To assess the feasibility of using intra-tumoral PF-3512676 in combination with local radiation as a therapy for lowgrade b-cell lymphoma.

Inclusion Criteria:

• Biopsy confirmed low-grade B-cell lymphoma diagnosed as follicular grade 1 or 2, marginal zone or small lymphocytic lymphoma of any initial stage.

• Patients may be either treatment-naïve; relapsed from; or refractory to prior therapy. (15 treatment-naïve and 15 relapsed/refractory patients will be enrolled)

• Patients must have at least one site of disease that is accessible for intratumoral injection of PF-3512676 percutaneously

• Tumor specimens must be available for immunological studies either from a previous biopsy or a new biopsy obtained before the initiation of the study.

• Patients must have measurable disease other than the injection site or biopsy site.

• Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 1

• Karnofsky Performance Status (KPS) of ≥ 70

• ≥ 18 years of age

• White blood cells (WBC) ≥ 2,000/uL

• Platelet count ≥ 75,000/mm³

• Absolute neutrophil count (ANC) ≥ 1000

• Serum creatinine ≤ 2.0 mg/dL.

• Bilirubin ≤ 1.5 mg/dL

• Serum glutamic oxalocetic transaminase (SGOT) / serum glutamic pyruvic transaminase (SGPT) ratio < 3 x upper limit of normal (ULN)

• Required wash out periods for prior therapy:

  • Topical therapy: 2 weeks
  • Chemotherapy: 4 weeks
  • Radiotherapy: 4 weeks
  • Other investigational therapy: 4 weeks
  • Rituximab: 12 weeks

• Patients of reproductive potential and their partners must agree to use an effective (>90% reliability) form of contraception during the study and for 4 weeks following the last study drug administration.

• Women of reproductive potential must have a negative urine pregnancy test.

• Life expectancy > 4 months.

• Able to comply with the treatment schedule.

• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Pre-existing autoimmune or antibody mediated disease including:

  • Systemic lupus, erythematosus
  • Rheumatoid arthritis
  • Multiple sclerosis
  • Sjogren's syndrome
  • Autoimmune thrombocytopenia, but excluding controlled thyroid disease
  • Presence of autoantibodies without clinical autoimmune disease.

• Known history of human immunodeficiency virus (HIV).

• Patients with active infection or with a fever > 38.5 C within 3 days prior to the first scheduled treatment.

• Central nervous system (CNS) metastases

• Prior malignancy (active within 5 years of screening) except basal cell or completely excised non-invasive squamous cell carcinoma of the skin, or in situ squamous cell carcinoma of the cervix.

• History of allergic reactions attributed to compounds of similar composition to PF-3512676

• Current anticoagulant therapy [aspirin (ASA) ≤ 325 mg per day allowed]

• Significant cardiovascular disease [ie, New York Heart Association (NYHA) class 3 congestive heart failure; myocardial infarction with the past 6 months; unstable angina; coronary angioplasty with the past 6 months; uncontrolled atrial or ventricular cardiac arrhythmias].

• Pregnant or lactating.

• Any other medical history, including laboratory results, deemed by the investigator to be likely to interfere with their participation in the study, or to interfere with the interpretation of the results.