A Phase I Study of Intratumoral Injections of CpG-STAT3 siRNA (CAS3/SS3) in Combination With Local Radiation in Patients With Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma (NHL)
This phase I trial identifies the best dose and side effects of CpG-STAT3 siRNA CAS3/SS3 (CAS3/SS3) in combination with localized radiation therapy in treating patients with B-cell non-Hodgkin lymphoma that has come back (relapsed) or does not respond to treatment (refractory). CAS3/SS3 simultaneously targets two molecules, TLR9 receptor and STAT3. This investigational drug combines a CpG oligonucleotide and an siRNA in one molecule that act together to interfere with the ability of the cancer cells to grow. Radiation therapy uses high energy x-rays to kill cancer cells and shrink tumors. Giving CAS3/SS3 with localized radiation therapy may kill more cancer cells.
• All subjects must have the ability to understand and the willingness to sign a written informed consent
• Age 18 and older
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (corresponds to Karnofsky Performance Status \[KPS\] of \>= 70)
• Life expectancy greater than 16 weeks
• Relapsed/refractory disease; patients must have failed \>= 2 prior systemic therapies and have no treatment options known to provide clinical benefit
• Biopsy confirmed relapsed or refractory B-cell lymphoma of the following subtypes; patients with a partial response to a previous treatment are allowed.
‣ Follicular grade 1 or 2, or 3 marginal zone or small lymphocytic lymphoma
⁃ Diffuse large B-cell lymphoma, non-germinal center B-cell like (GCB) type determined by immunohistochemistry using Han's algorithm
⁃ Mantle cell lymphoma
• Patients must have at least two separate tumor sites, one of which is at least 2 cm in diameter and peripherally accessible and amenable for intratumoral injection of CAS3/SS3 with stabilization by palpation, and the other is at least 1.5 cm in diameter
• Tumor specimens must be available for immunological studies either from a previous biopsy or a new biopsy obtained before the initiation of the study. Paraffin-embedded specimens are acceptable
• Required wash out periods for prior therapy:
‣ Topical therapy: 2 weeks
⁃ Chemotherapy: 4 weeks
⁃ Radiotherapy: 4 weeks
⁃ Other investigational therapy: 4 weeks
⁃ Monoclonal antibody or immunotherapy: 4 weeks
⁃ Targeted therapies: 4 weeks
⁃ Allogeneic transplant: 6 months
• Absolute neutrophil count (ANC) \>= 1,000/mm\^3
‣ NOTE: Growth factor is not permitted within 14 days of ANC assessment unless cytopenia is secondary to disease involvement
• Platelets \>= 75,000/mm\^3
‣ NOTE: Platelet transfusions are not permitted within 14 days of platelet assessment unless cytopenia is secondary to disease involvement
• Hemoglobin \>= 8 g/dl
• Total serum bilirubin (mg/dL): =\< 1.5 x upper normal limit (ULN)
• Aspartate aminotransferase (AST) \< 3 x ULN without liver metastasis and \< 5 x ULN with liver metastasis
• Alanine aminotransferase (ALT) \< 3 x ULN without liver metastasis and \< 5 x ULN with liver metastasis
• Adequate renal function as determined by serum creatinine =\< 2.0 mg/dL or creatinine clearance of \>= 50 mL/min per the Cockcroft-Gault formula
• International normalized ratio (INR) OR prothrombin (PT) =\< 1.5 x ULN
• Activated partial thromboplastin time (aPTT) =\< 1.5 x ULN
• Female of childbearing potential: serum pregnancy test
• Cardiac function 12-lead electrocardiogram (ECG) to confirm the absence of clinically significant arrhythmias
• Left ventricular ejection fraction (LVEF) \>= 45%
• Oxygen saturation on room air of \>= 92%
• The effects of CAS3/SS3 on the developing fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation. Should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately