Intratumoral Injection of SD-101, an Immunostimulatory CpG, in Combination With BMS-986178 and Local Radiation in Low-Grade B-Cell Lymphomas
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Ronald Levy
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Number of participants experiencing Dose-limiting Toxicities (DLT) within 8 weeks of treatment initiation
研究概览
简要总结
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.
详细描述
PRIMARY OBJECTIVES:
I. To determine the safety and tolerability of TLR9 agonist SD-101 (SD-101) in combination with anti-OX40 antibody BMS 986178 (BMS-986178) and local low-dose radiation in patients with low-grade B-cell lymphoma. Adverse events and grades to be assessed by Common Terminology Criteria for Adverse Events (CTCAE) II. To determine the recommended phase 2 dose (RP2D) of BMS-986178 in combination with intratumoral SD-101 and radiation in patients with low-grade B-cell lymphoma.
SECONDARY OBJECTIVES:
I. To evaluate preliminary efficacy by assessing overall response rate and progression-free survival after treatment with intratumoral SD-101 in combination with BMS-986178 and radiation in patients with low-grade B-cell lymphoma.
OUTLINE: This is a phase I study of the combination of TLR9 agonist SD-101, anti-OX40 antibody BMS 986178, and local low-dose radiation therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 cause)
- •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
排除标准
- •Currently transformed lymphoma, high-risk mantle cell lymphoma, or gastric MALT lymphoma.
- •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
研究组 & 干预措施
Treatment (radiation therapy, SD-101, BMS-986178)
Patients receive radiation therapy on days 1-2, TLR9 agonist SD-101 and anti-OX40 antibody BMS-986178 intratumorally on days 2, 9, 16, 23, and 30, and anti-OX40 antibody BMS-986178 IV on days 2, 30, 58, 86, 114, and 142 in the absence of disease progression or unacceptable toxicity.
干预措施: Anti-OX40 Antibody BMS 986178 (Biological)
Treatment (radiation therapy, SD-101, BMS-986178)
Patients receive radiation therapy on days 1-2, TLR9 agonist SD-101 and anti-OX40 antibody BMS-986178 intratumorally on days 2, 9, 16, 23, and 30, and anti-OX40 antibody BMS-986178 IV on days 2, 30, 58, 86, 114, and 142 in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (radiation therapy, SD-101, BMS-986178)
Patients receive radiation therapy on days 1-2, TLR9 agonist SD-101 and anti-OX40 antibody BMS-986178 intratumorally on days 2, 9, 16, 23, and 30, and anti-OX40 antibody BMS-986178 IV on days 2, 30, 58, 86, 114, and 142 in the absence of disease progression or unacceptable toxicity.
干预措施: Radiation Therapy (Radiation)
Treatment (radiation therapy, SD-101, BMS-986178)
Patients receive radiation therapy on days 1-2, TLR9 agonist SD-101 and anti-OX40 antibody BMS-986178 intratumorally on days 2, 9, 16, 23, and 30, and anti-OX40 antibody BMS-986178 IV on days 2, 30, 58, 86, 114, and 142 in the absence of disease progression or unacceptable toxicity.
干预措施: TLR9 Agonist SD-101 (Drug)
结局指标
主要结局
Number of participants experiencing Dose-limiting Toxicities (DLT) within 8 weeks of treatment initiation
时间窗: Up to 8 weeks
Dose-limiting toxicities (DLTs) as assessed as the following hematologic toxicities (grades per CTCAE) in all participants receiving at least 1 intratumoral (IT) injection of SD-101 and at least 1 dose of BMS-986178 (not including events due to disease progression or definitively unrelated to study drugs): * Febrile neutropenia * Thrombocytopenia Grade 4 or Grade 3 with bleeding or platelet transfusion * Anemia Grade 4 * Non-hematological toxicity ≥ grade 3, except: * Alopecia controlled by medical management * Nausea controlled by medical management * Grade 3 or 4 electrolyte abnormalities not associated with adverse events, persist \< 72 hours, and either spontaneously resolve or respond to intervention. * Grade 3 or 4 elevation of amylase or lipase not associated with pancreatitis * Grade 3 endocrinopathy * Grade 3 infusion reaction returning to ≤ Grade 1 in \< 6 hours * Grade 3 skin rash not requiring systemic steroid or other immunosuppressive therapy
次要结局
- Overall Response Rate (ORR)(Up to 96 weeks)
- Progression-Free Survival (PFS)(up to 96 weeks)
研究者
Ronald Levy
Robert K. and Helen K. Summy Professor
Stanford University