In Situ Vaccine for Low-Grade Lymphoma: Combination of Intratumoral Flt3L and Poly-ICLC With Low-Dose Radiotherapy

Inclusion Criteria:

* Biopsy-confirmed low-grade B-cell lymphoma or cutaneous T cell lymphoma; specifically, follicular grade 1, 2, or 3A, marginal zone or small lymphocytic lymphoma, or mycosis fungoides of any initial stage. Patients in cohort A must be relapsed/refractory after at least one prior systemic therapy and patients in cohort B must have had no prior systemic therapy.
* Patients must have at least one site of disease that is accessible for intratumoral injection percutaneously (e.g. inguinal, axillary, cervical, or subcutaneous).
* Tumor specimens must be available for immunological studies, either from a previous biopsy or a new biopsy obtained before the initiation Day 1 of the study.
* Patients must have measurable disease other than the injection site or biopsy site, i.e. greater than 1.5 cm bi-dimensionally on standard computed tomography imaging.
* ECOG Performance Status of 1 or better (corresponds to Karnofsky Performance Status (KPS) of ≥ 70)
* Patients must be 18 years of age or older.
* Adequate bone marrow function: WBC ≥ 2,000/μL; platelet count ≥ 75,000/mm3; ANC ≥ 1000/μL.
* Adequate renal function: serum creatinine ≤ 2.0mg/dL.
* Adequate hepatic function: bilirubin ≤ 1.5 mg/dL; SGOT/SGPT \< 3 x upper limit of normal
* Required wash out periods for prior therapy (for cohort B):

  1. Topical therapy: 2 weeks
  2. Chemotherapy: 4 weeks
  3. Radiotherapy: 4 weeks
  4. Other investigational therapy: 4 weeks
  5. 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.
* 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, history of uveitis. Patients with controlled thyroid disease, or the presence of auto-antibodies without clinical autoimmune disease, are permitted on study.
* Known history of human immunodeficiency virus (HIV).
* Patients with active infection.
* Known 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 to compounds of similar composition to either CDX-301 or poly-ICLC.
* Current anticoagulant therapy. (ASA ≤ 325 mg per day is 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 abnormalities, deemed by the investigator to be likely to interfere with their participation in the study, or to interfere with the interpretation of the results.