A Phase II, Multicenter Clinical Study of Sintilimab Combined With Rituximab Followed by R-CHOP Regimen in Patients With Previously Untreated Primary Mediastinal Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- Complete response rate of Sintilimab combined with rituximab followed by R-CHOP regimen
研究概览
简要总结
The goal of this clinical study is to evaluate the efficacy and safety of sintilimab combined with rituximab followed by R-CHOP regimen in treatment-naïve patients with primary mediastinal diffuse large B-cell lymphoma. The main questions it aims to answer are:
- Objective response rate of sintilimab combined with rituximab
- Objective response rate after R-CHOP regimen
详细描述
Participants will first receive sintilimab plus rituximab for 2 cycles, followed by interim PET-CT assessments. If patients achieve CR or CMR, they will continue to receive 2 courses of sintilimab plus rituximab, followed by 4 cycles of R-CHOP. Patients will receive 6 courses of R-CHOP if they do not achieve CR or CMR after 2 cycles of sintilimab plus rituximab. Patients will undergo PET-CT assessment and will receive 6 cycles of maintenance treatment with nintedanib if CR/CMR/PR is achieved and will be withdrawn from the study if SD/PD occurs. Total treatment cycles will not exceed 14 cycles
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary participation in clinical study and fully understand, informed consent and sign informed consent form (ICF);
- •Age ≥ 18 years and ≤ 75 years at the time of signing the ICF.
- •treatment-naïve, no anti-lymphoma therapy.
- •Primary mediastinal DLBCL was confirmed histopathologically at the study site.
- •Lugano clinical stage I-IV.
- •International Prognostic Score (IPI) 0-
- •Available tumor tissue samples obtained by previous or fresh core needle aspiration or resection.
- •ECOG score of 0-
- •Expected survival greater than 12 months.
- •Must have at least 1 evaluable or measurable lesion that meets the LYRIC 2016 response evaluation criteria for malignant lymphoma.
- •Adequate organ and bone marrow function, no severe hematopoietic dysfunction and heart, lung, liver, kidney, thyroid dysfunction and immunodeficiency.
- •Pulse oximetry values > 92% at rest.
- •Women of childbearing potential (WOBCP) must have a negative serum pregnancy test within 7 days before the first dose; WOBCP or men and their WOBCP partners should agree to use effective contraception from signing the ICF until 6 months after the last dose of study drug.
排除标准
- •Primary central nervous system lymphoma or secondary central nervous system involvement.
- •previous treatment with immune checkpoint inhibitors (PD-1, PD-L1, CTLA-4, etc.).
- •3 History of severe allergic or allergic reactions to humanized or murine monoclonal antibodies.
- •Patients with active autoimmune diseases that require systemic treatment within the past two years; patients with autoimmune diseases that do not require systemic treatment within the past two years may be enrolled.
- •Subjects requiring systemic glucocorticoid therapy or other immunosuppressive therapy for a condition within 14 days prior to starting study treatment [subjects are allowed to be treated with topical, ocular, intra-articular, intranasal, and inhaled glucocorticoids (with minimal systemic absorption); short-term (≤ 7 days) glucocorticoid prophylaxis (e.g., contrast agent allergy) or for the treatment of non-autoimmune diseases (e.g., delayed hypersensitivity due to contact allergens) is allowed]. Low dose steroid debulking therapy for large tumor burden may be excluded (prednisone 30 mg bid × 5 days or equivalent doses of other steroids are allowed).
- •Other malignancies within the past 5 years, except for radically treated cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, breast carcinoma in situ, and cervical carcinoma in situ.
- •Systemic anti-tumor therapy within 28 days before starting study treatment, including chemotherapy, immunotherapy, biological therapy (tumor vaccine, cytokines, or growth factors to control cancer), etc.
- •Major surgery within 28 days or radiation therapy within 90 days prior to starting study treatment.
- •Anti-cancer Chinese herbal medicine or Chinese patent medicine within 7 days prior to starting study treatment.
- •Administration of live vaccines (except attenuated influenza vaccines) within 28 days prior to starting study treatment.
- •Patients with known history of human immunodeficiency virus infection and/or acquired immunodeficiency syndrome.
- •Patients with active chronic hepatitis B or active hepatitis C. Patients who are positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies at screening must be further tested for hepatitis B virus (HBV) DNA titer (not more than 2500 copies/mL or 1000 IU/mL) and HCV RNA (not more than the lower limit of detection of the assay).
- •Any active infection requiring systemic anti-infective therapy within 14 days prior to starting study treatment.
- •Pregnant or lactating women.
- •Have uncontrolled concomitant disease.
- •Patients with a previous history of mental illness; those who are incapacitated or have limited behavioral ability.
研究组 & 干预措施
Sintilimab plus rituximab followed by R-CHOP regimen
Participants will first receive sintilimab plus rituximab for 2 cycles, followed by interim PET-CT assessments. If patients achieve CR or CMR, they will continue to receive 2 courses of sintilimab plus rituximab, followed by 4 cycles of R-CHOP. Patients will receive 6 courses of R-CHOP if they do not achieve CR or CMR after 2 cycles of sintilimab plus rituximab. Patients will undergo PET-CT assessment and will receive 6 cycles of maintenance treatment with nintedanib if CR/CMR/PR is achieved and will be withdrawn from the study if SD/PD occurs. Total treatment cycles will not exceed 14 cycles.
干预措施: Sintlimab+Rituximab follwed by R-CHOP(Cyclophosphamide, doxorubicin, vincristine, prednisone) (Drug)
结局指标
主要结局
Complete response rate of Sintilimab combined with rituximab followed by R-CHOP regimen
时间窗: 36 months
Investigator-assessed complete response rate of Sintilimab combined with rituximab followed by R-CHOP regimen. Complete response ratewas determined on the basis of investigator assessments according to the Lymphoma response to immunomodulatory therapy criteria (LYRIC) for Malignant Lymphoma, 2016. Tumor assessments were performed with CT/MRI with or without PET.Complete response was defined as the disappearance of all evidence of disease, regression of measurable disease, and no new sites.
次要结局
- Objective response rate of Sintilimab combined with rituximab followed by R-CHOP regimen(36 months)
- Progression-free survival of whole cohort(72 months)
- Duration of response in responding patients(72 months)
- Overall survival of whole cohort(72 months)
- Incidence of Adverse event(72 months)
研究者
Huiqiang Huang
Professor
Sun Yat-sen University