TLR9 Agonist SD-101, Ibrutinib, and Radiation Therapy in Treating Patients With Relapsed or Refractory Grade 1-3A Follicular Lymphoma

Inclusion Criteria

• •Biopsy confirmed Grade 1 or 2, or 3A follicular lymphoma; mantle cell lymphoma; or marginal zone lymphoma. Subjects must have relapsed from or are refractory to prior therapy.
• •Subjects must have at least one site of disease that is accessible for intratumoral injection of SD 101 (diameter ≥ 10mm), percutaneously.
• •Subjects must have at least one site of measurable disease (see Section 10.2.2 for definition of measurable disease) other than the injection site which is not included in the radiation field.
• •ECOG Performance Status of 0 or 1
• •Subjects must be 18 years of age or older.
• •Required values for initial laboratory tests:
• •1. Absolute neutrophil count (ANC) ≥ 1000/mm3 independent of growth factor support
• •2. Platelets: ≥ 100,000/mm3 or ≥ 50,000/mm3 if bone marrow involvement independent of transfusion support in either situation
• •3. Hemoglobin: ≥ 8 g/dL (may be transfused)
• •4. Creatinine: Creatinine clearance \> 25 mL/min
• •5. AST/ALT: ≤ 3 x ULN
• •6. Bilirubin: ≤ 1.5 x ULN (except for subjects with Gilbert's Syndrome or of non hepatic origin)
• •Must be at least 4 weeks since treatment with standard or investigational chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, and 8 weeks since any monoclonal antibodies or immunotherapy, and recovered from any clinically significant toxicity experienced during treatment.
• •Women of childbearing potential and men who are sexually active must be practicing a highly effective method of birth control during and after the study consistent with local regulations regarding the use of birth control methods for subjects participating in clinical trials. Men must agree to not donate sperm during and after the study. For females, these restrictions apply for 1 month after the last dose of study drug. For males, these restrictions apply for 3 months after the last dose of study drug.
• •Women of childbearing potential must have a negative serum (beta human chorionic gonadotropin \[β-hCG\]) or urine pregnancy test at Screening. Women who are pregnant or breastfeeding are ineligible for this study.
• •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.