Risk-based, Response-adapted, Phase II Open-label Trial of Nivolumab + Brentuximab Vedotin (N + Bv) for Children, Adolescents, and Young Adults With Relapsed/Refractory (R/R) CD30 + Classic Hodgkin Lymphoma (cHL) After Failure of First-line Therapy, Followed by Brentuximab + Bendamustine (Bv + B) for Participants With a Suboptimal Response (CheckMate 744: CHECKpoint Pathway and Nivolumab Clinical Trial Evaluation)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 72
- 试验地点
- 73
- 主要终点
- Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Blinded Independent Centralized Review (BICR) - Cohort 1
研究概览
简要总结
The purpose of this study is to determine whether nivolumab plus brentuximab vedotin (followed by brentuximab vedotin plus bendamustine in patient with suboptimal response) is safe and effective in treating patients with Hodgkin's lymphoma (cHL). Eligible patients are children, adolescents, and young adults relapsed or refractory to first line.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 30 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Classic Hodgkin Lymphoma (cHL), relapsed or refractory
- •Minimal limitation on activities of daily living as measured by Karnofsky ≥ 50 for participants > 16 years of age or Lansky ≥ 50 for participants ≤ 16 years of age.
- •One prior anti-cancer therapy that did not work
排除标准
- •Active, known, or suspected autoimmune disease or infection
- •Active cerebral/meningeal disease related to the underlying malignancy
- •More than one line of anti-cancer therapy or no treatment at all
- •Received a stem cell transplant for Hodgkin Lymphoma and/or a solid organ transplant
- •Prior treatment with any drug that targets T cell co-stimulation pathways (such as checkpoint inhibitors)
- •Other protocol defined inclusion/exclusion criteria apply
研究组 & 干预措施
Nivolumab + brentuximab vedotin
干预措施: Nivolumab (Biological)
Nivolumab + brentuximab vedotin
干预措施: brentuximab vedotin (Biological)
brentuximab vedotin + bendamustine
干预措施: brentuximab vedotin (Biological)
brentuximab vedotin + bendamustine
干预措施: bendamustine (Biological)
结局指标
主要结局
Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Blinded Independent Centralized Review (BICR) - Cohort 1
时间窗: From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).
The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved best response of CMR. Complete metabolic response (CMR): * Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Participants who stopped study treatment early for toxicity without a CMR were evaluable. Confidence interval is based on the Clopper and Pearson method
Event-free Survival (EFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR) - Cohort 1
时间窗: At 3 years post first dose of study therapy
Event Free Survival (EFS) is the time from the first treatment to the earliest occurrence of composite events including: Disease progression (PD), Failure to achieve complete metabolic response (CMR) after 4 cycles of N+Bv and 2 cycles of Bv+B, Secondary malignancy, Death . PD : Lymph Nodes and Lesions: new growth or increase of \>= 50% in size from nadir. New or growing lesions outside the lymph nodes. Spleen: Significant increase in spleen size, either from a previously enlarged state or from normal size. New Lesions: Yes Bone Marrow: New or returning FDG-avid disease CMR: Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale New lesions: No Bone marrow: No FDG-avid disease Participants without an "event" were censored at the last tumor assessment. Those who started subsequent anticancer therapy without a prior "event" were censored at the last tumor assessment prior to or upon starting subsequent therapy. Based on Kaplan-Meier Estimates.
Complete Metabolic Response (CMR) Rate at Any Time Prior to High Dose Chemotherapy Followed by Autologous Stem Cell Treatment (HDCT/ASCT) by Blinded Independent Centralized Review (BICR) - Cohort 2
时间窗: From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks)
The complete metabolic response (CMR) rate is defined as the percent of all response-evaluable participants who, assessed by the BICR, achieved best response of CMR. Complete metabolic response (CMR): * Lymph nodes/extralymphatic sites: Score 1, 2, 3 with/without residual mass on 5-point scale * New lesions: No * Bone marrow: No FDG-avid disease Participants who came off study treatment early for toxicity without a CMR were evaluable. Confidence interval is based on the Clopper and Pearson method
次要结局
- The Number of Participants With Serious Adverse Events (SAEs)(From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months))
- Duration of Response (DOR) by Blinded Independent Centralized Review (BICR)(From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months))
- Complete Metabolic Response (CMR) Rate at Any Time Prior to Radiation Therapy by Investigator - Cohort 1(From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks).)
- Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Blinded Independent Centralized Review (BICR)(From first dose to PMR or CMR within 4 cycles of therapy, or the completion of four cycles of therapy (N+Bv x4) (up to approximately 12 weeks).)
- Progression Free Survival (PFS) Rate at 3 Years by Blinded Independent Centralized Review (BICR)(At 3 years post first dose of study therapy)
- Progression Free Survival (PFS) Rate at 3 Years by Investigator(At 3 years post first dose)
- The Number of Participants With Abnormal Laboratory Values for Specific Thyroid Tests(From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months))
- The Number of Participants With Abnormal Laboratory Values for Liver Tests(From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months))
- Number of Participants With Abnormal Vital Signs Reported as Adverse Events(From first dose to 100 days after last dose of study therapy (assessed for an average of 7 months up until a maximum of 10 months).)
- Event-free Survival (EFS) Rate at 3 Years by Investigator - Cohort 1(At 3 years post first dose of study therapy)
- Complete Metabolic Response (CMR) Rate at Any Time Prior to High Dose Chemotherapy Followed by Autologous Stem Cell Treatment (HDCT/ASCT) by Investigator - Cohort 2(From first dose to complete metabolic response or the completion of six cycles of therapy (up to approximately 18 weeks))
- Overall Response Rate (ORR) Following 4 Cycles of Nivolumab + Brentuximab Vedotin Treatment by Investigator(From first dose to PMR or CMR within 4 cycles of therapy, or the completion of four cycles of therapy (N+Bv x4) (up to approximately 12 weeks).)
- Duration of Response (DOR) by Investigator(From first dose until disease progression, start of subsequent anti-cancer therapy, or or death due to any cause (up to approximately 86 months))
- The Number of Participants With Adverse Events (AEs)(From first dose to 30 days post last dose (an average of 4 months up until a maximum of 7 months).)