• Local and systemic anti-tumor efficacy. [ Time Frame: baseline, week 6, week 12 - all patients; weeks 2, 3, 4 - MF patients only ] [ Designated as safety issue: No ]
• Tumor-specific humoral and cellular immune responses. [ Time Frame: baseline, week 6, week 12 - all patients; weeks 2, 3, 4 - MF patients only ] [ Designated as safety issue: No ]

• 1. To determine local and systemic anti-tumor efficacy.
• 2. To evaluate tumor-specific humoral and cellular immune responses.

This is a single institution phase I / II trial to evaluate the safety, feasibility and efficacy of CpG injections (4 intratumoral injections followed by 6 peri-tumoral injections) combined with local irradiation in patients with recurrent low-grade lymphomas.

Patients will receive low-dose radiotherapy to a single tumor site on days 1 and 2 (2 Gy each day). CpG injections will be administered into the same tumor site within the 24 hours before and the 24 hours after the radiation, and on days 8 and 15. Weekly doses of CpG will be then administered subcutaneously in the region of previous injections for 6 additional doses.

• Drug: CPG 7909
• Procedure: Local radiation

Inclusion Criteria:Patients must meet all of the following criteria in order to be eligible for entry into the trial.

• Biopsy confirmed low-grade B-cell lymphoma of any initial stage or mycosis fungoides of stage IB-IVA. B-cell lymphoma patients must have failed at least one prior treatment. Mycosis fungoides patients must have failed or have been intolerant of at least 2 topical or one systemic treatment.
• Patients must have at least one site of disease that is accessible for intratumoral injection of CpG percutaneously
• Tumor specimens must be available for immunological studies either from a previous biopsy or a new biopsy obtained before the initiation of the treatment.
• Patients must have measurable disease other than the injection site or biopsy site.
• 18 years of age or older
• Karnofsky Performance Status (KPS) of > 70.
• Adequate bone marrow function: WBC>4,000uL, hemoglobin > 10g/dL; platelet count >100,000/mm3; ANC> 1000.
• Adequate hepatic function: bilirubin <= 1.5 mg/dL; SGOT/SGPT<3xupper limit of normal
• Adequate renal function: serum creatinine <= 2.0mg/dL.

• Required wash out periods for prior therapy:

  • Topical therapy: 2 weeks
  • Chemotherapy: 4 weeks
  • Radiotherapy (including photo therapy): 4 weeks
  • Systemic biological therapy for mycosis fungoides: 4 weeks
  • Other investigational therapy: 4weeks
  • 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 negative urine pregnancy test.
• Life expectancy greater than 4 months.
• Able to comply with the treatment schedule.

Exclusion Criteria:A patient may not be enrolled in the trial if any of the following criteria are met.

• 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, or the presence of autoantibodies without clinical autoimmune disease.
• Known history of human immunodeficiency virus (HIV), hepatitis B or hepatitis C (active, prior treatment, or both).
• Patients with active infection or with a fever >38.50 C within three days prior to the first scheduled treatment.
• 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 CpG 7909
• Current anticoagulant therapy (ASA<= 325mg/day allowed).
• Significant cardiovascular disease (i.e. 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.

• Lymphoma Research Foundation
• American Society of Clinical Oncology
• National Institutes of Health (NIH)