TLR9 Agonist SD-101, Anti-OX40 Antibody BMS 986178, and Radiation Therapy in Treating Patients With Low-Grade B-Cell Non-Hodgkin Lymphomas

Not Recruiting

Trial ID: NCT03410901


This phase I trial studies the side effects and best dose of the anti-OX40 antibody BMS-986178 when given together with the TLR9 agonist SD-101 and radiation therapy in treating patients with low-grade B-cell Non-Hodgkin lymphomas. TLR9 agonist SD-101 may stimulate the immune system in different ways and stop cancer cells from growing. Anti-OX40 antibody is a monoclonal antibody that enhances the activation of T cells, immune cells that are important for fighting tumors Radiation therapy uses high energy x-rays to kill cancer cells and may make them more easily detected by the immune system. Giving TLR9 agonist SD-101 together with anti-OX40 antibody BMS 986178 and radiation therapy may work better in treating patients with low-grade B-cell non-hodgkin lymphomas.

Official Title

Intratumoral Injection of SD-101, an Immunostimulatory CpG, in Combination With BMS-986178 and Local Radiation in Low-Grade B-Cell Lymphomas

Stanford Investigator(s)

Ronald Levy, MD
Ronald Levy, MD

Robert K. and Helen K. Summy Professor in the School of Medicine

Michael Khodadoust
Michael Khodadoust

Assistant Professor of Medicine (Oncology) and of Dermatology

Richard Hoppe
Richard Hoppe

Henry S. Kaplan-Harry Lebeson Professor of Cancer Biology


Inclusion Criteria:

   - Biopsy confirmed low-grade B-cell lymphoma, excluding gastric MALT lymphoma, high-risk
   mantle cell lymphoma, and currently transformed lymphoma

   - Patients must have at least one site of disease (cervical, axillary, inguinal, or
   subcutaneous) that is accessible for intratumoral injection of SD-101 (diameter ≥10mm)
   percutaneously and presents a low risk for complications from direct injections.

   - Patients must have at least one site of measurable disease, other than the injection
   site, which is not included in the radiation field

   - Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

   - Absolute neutrophil count (ANC) >= 1000/mm^3 independent of growth factor support

   - Platelets: >= 100,000/mm^3 or >= 50,000/mm^3 if known or suspected bone marrow
   involvement, independent of transfusion support in either situation

   - Hemoglobin: >= 8 g/dL (may be transfused)

   - Creatinine: Creatinine clearance > 25 ml/min

   - Aspartate aminotransferase (AST)/alanine aminotransferase (ALT): =< 3 x upper limit of
   normal (ULN)

   - Bilirubin: =< 1.5 x ULN (except for subjects with Gilbert's Syndrome or of non-hepatic

   - Must be at least 4 weeks since treatment with standard or investigational
   chemotherapy, biochemotherapy, surgery, radiation, cytokine therapy, 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 sexually active women of childbearing potential, these restrictions
   apply for 5 months after the last dose of study drug; for sexually active men, these
   restrictions apply for 7 months after the last dose of study drug

   - Women of childbearing potential must have a negative serum (beta-human chorionic
   gonadotropin [beta-hCG]) or urine pregnancy test at screening, within 24 hours of the
   first dose of anti-OX40 antibody, and every four weeks while on study treatment; women
   who are pregnant or breastfeeding are ineligible for this study

   - Life expectancy greater than 3 months

   - Ability to comply with the treatment schedule

   - Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria:

   - Currently transformed lymphoma, high-risk mantle cell lymphoma, or gastric MALT

   - Need for immediate treatment or cytoreduction.

   - No easily accessible site for direct percutaneous injection with low-risk for
   potential complications.

   - Autoimmune disease requiring treatment within the last 5 years including systemic
   lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome,
   autoimmune thrombocytopenia, uveitis, or other if clinically significant

   - Major surgery within 4 weeks of enrollment, or a wound that has not fully healed

   - Vaccinated with live, attenuated vaccines within 4 weeks of enrollment

   - Known history of human immunodeficiency virus (HIV) or active hepatitis C virus or
   active hepatitis B virus infection or any uncontrolled active systemic infection

   - Known central nervous system (CNS) lymphoma

   - Patients with a history of prior malignancy with the exception of non-melanoma skin
   cancer, stage 1 prostate cancer that does not require treatment, or other malignancy
   that has undergone potentially curative therapy with no evidence of disease for the
   last 2 years and that is deemed by the investigators to be at low risk for recurrence.
   In situ cancer of any type and noninvasive follicular thyroid neoplasm with
   papillary-like nuclear features (NIFTP) is not an exclusion, though if surgery or
   other definitive intervention is planned, it should be completed prior to enrollment.

   - History of significant allergic reactions attributed to compounds of similar
   composition to SD-101 or BMS-986178

   - Treatment with an immunosuppressive regimen of corticosteroids or other
   immunosuppressive medication (e.g., methotrexate, rapamycin) within 30 days of study
   treatment; Note: patients may take up to 5 mg of prednisone or equivalent daily;
   topical and inhaled corticosteroids in standard doses are allowed

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

   - Pregnant or breast feeding

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


biological: Anti-OX40 Antibody BMS 986178

other: Laboratory Biomarker Analysis

radiation: Radiation Therapy

drug: TLR9 Agonist SD-101

Not Recruiting

Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305
Alyssa Michelle Kanegai

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