A Phase I/ II Study to Evaluate the Safety and Preliminary Efficacy of Nivolumab in Combination With Brentuximab Vedotin in Subjects With Relapsed Refractory Non Hodgkin Lymphomas With CD30 Expression (CheckMate 436: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation 436)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 145
- 试验地点
- 27
- 主要终点
- Safety Analysis - Number of Participants With Dose Limiting Toxicities (DLT) in the DLT Evaluation Phase
研究概览
简要总结
The purpose of this study is to determine whether Nivolumab, in combination with brentuximab vedotin, is safe and effective in patients with certain subtypes of non-Hodgkin's lymphomas with CD30 expression that have not responded to treatment or have come back. The subtypes we are studying are Diffuse Large B-Cell Lymphoma (DLBCL), Peripheral T-Cell Lymphoma (PTCL), Cutaneous T-Cell Lymphoma (CTCL), Primary Mediastinal Large B-Cell Lymphoma (PMBL) and Mediastinal Gray Zone Lymphoma (MGZL).
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
- 15 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsed/refractory diffuse large B cell lymphoma (DLBCL), relapsed/refractory peripheral T cell lymphoma (PTCL) (all subtypes excluding anaplastic large cell lymphoma), relapsed/refractory Cutaneous T cell lymphoma (CTCL) mycosis fungoides/sezary syndrome (MF/SS), relapsed/refractory primary mediastinal B lymphoma (PMBL), and relapsed/refractory mediastinal gray zone lymphoma (MGZL)
- •Expression of CD30
- •Subjects must be 18 years or older (≥ 15 years for PMBL)
排除标准
- •Known central nervous system (CNS) lymphomas; Active cerebral/meningeal disease related to the underlying malignancy
- •Active, known, or suspected autoimmune disease
研究组 & 干预措施
Nivolumab+Brentuximab Vedotin
Nivolumab+Brentuximab Vedotin dose as specified
干预措施: Nivolumab (Biological)
Nivolumab+Brentuximab Vedotin
Nivolumab+Brentuximab Vedotin dose as specified
干预措施: Brentuximab Vedotin (Drug)
结局指标
主要结局
Safety Analysis - Number of Participants With Dose Limiting Toxicities (DLT) in the DLT Evaluation Phase
时间窗: From first dose of treatment to 6 weeks after first dose
DLTs are defined as any study drug-related toxicity (brentuximab vedotin or nivolumab) that requires either a dose reduction or delay of more than 7 days of either study drug in Cycle 2 or delays the Cycle 3 Day 1 administration of combined treatment by more than 7 days.
Safety Analysis - Number of Participant Deaths
时间窗: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Number of participant Deaths
Safety Analysis - Number of Participants With Adverse Advents
时间窗: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a preexisting medical condition in a clinical investigation participant administered study drug and that does not necessarily have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (such as an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug.
Safety Analysis - Number of Participants With Serious Adverse Events
时间窗: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
A Serious Adverse Event (SAE) is any untoward medical occurrence that at any dose: * results in death * is life-threatening (defined as an event in which the participant was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe) * requires inpatient hospitalization or causes prolongation of existing hospitalization. * results in persistent or significant disability/incapacity * is a congenital anomaly/birth defect * is an important medical event
Safety Analysis - Number of Participants With Adverse Events Leading to Discontinuation
时间窗: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Number of participants with adverse events leading to discontinuation
Safety Analysis - Number of Participants With Adverse Events Leading to Dose Delay or Reduction
时间窗: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Number of participants with adverse events leading to dose delay or reduction
Safety Analysis - Number of Participants With Drug Related Adverse Events
时间窗: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Number of participants with Drug Related Adverse Events
Safety Analysis - Percentage of Participants With Thyroid Test Abnormalities
时间窗: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Percentage of participants with specific thyroid test abnormalities
Safety Analysis - Percentage of Participants With Liver Test Abnormalities
时间窗: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
Percentage of participants with specific Liver test abnormalities
Objective Response Rate (ORR)
时间窗: CTCL: 20 Months, PTCL: 26.5 Months, DLBCL: 26 Months, MGZL: 30 Months and PMBL 25.5 Months
The percentage of participants with a best overall response (BOR) of CR or PR. DLBCL, PTCL, PMBL \& MGZL complete and partial response are outlined in the Lugano Classification 2014 and Lymphoma Response to Immunomodulatory therapy Criteria. CTCL complete and partial response are defined in The consensus Global Response Score assessment.
次要结局
- Duration of Response (DOR)(From the first patient first visit to 8 months after the last patient first visit (up to 48 months))
- Complete Response Rate (CRR)(From first dose to the date of initial objectively documented progression or the date of subsequent therapy, whichever occurs first (up to 48 months))
- Duration of Complete Response(From first dose to the date of relapse or death due to any cause, whichever occurs first. (about 48 months))
- Progression Free Survival (PFS)(From first dose of study drug until the date of first documented evidence of progressive disease (or relapse for participants who experience CR during the study) or death due to any cause, whichever comes first. (about 48 months))
- Overall Survival (OS)(From the first patient first visit to 8 months after the last patient first visit (about 48 months))