Multiple Part Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma Subjects
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Seagen Inc.
- 入组人数
- 255
- 试验地点
- 76
- 主要终点
- Febrile Neutropenia (FN) Rate (Part A)
研究概览
简要总结
This trial will study two treatment combinations for classical Hodgkin lymphoma (cHL). This trial will find out if these two treatment combinations work to treat cHL. It will also find out what side effects occur. A side effect is anything the drug does besides treating cancer. This study will have three parts (Parts A, B, and C).
The drugs used in Part A are a combination of targeted anticancer drug (brentuximab vedotin) and three chemotherapy drugs (doxorubicin, vinblastine, and dacarbazine). These four drugs are called "A+AVD." Participants will be treated with granulocyte colony stimulating factor (G-CSF) following every dose of A+AVD for 6 cycles of treatment (12 doses).
Part A will look at whether the A+AVD drug combination reduces the number of participants who experience the side effect of febrile neutropenia. Febrile neutropenia is a very low white blood cell count and a fever, which can be life threatening.
Parts B and C will use drug combination of brentuximab vedotin, plus nivolumab, doxorubicin, and dacarbazine. These four drugs are called "AN+AD." Parts B and C will study how well the drugs work to treat cHL and what side effects they cause.
详细描述
This study will have three parts.
Part A of the study is designed to evaluate the incidence of febrile neutropenia, efficacy, and dose intensity in participants with advanced stage classical Hodgkin lymphoma (cHL) receiving granulocyte colony stimulating factor primary prophylaxis (G-PP) administration during treatment with frontline A+AVD. In Part A, participants will be treated with granulocyte colony stimulating factor (G-CSF) following every dose of A+AVD for 6 cycles of treatment. Participants will be treated using institutional standard of care practices for the majority of treatment decisions.
Part B is designed to evaluate the combination of brentuximab vedotin, nivolumab, doxorubicin, and dacarbazine (AN+AD) as frontline treatment in participants with advanced cHL. In Part B, participants will be given AN+AD combination for 6 cycles of treatment. This part of the trial will look at whether this combination of drugs is effective and tolerable in participants with Stage II with bulky mediastinal disease and Stage III or IV cHL.
Part C is designed to evaluate AN+AD as frontline treatment in participants with early stage cHL. In Part C, participants will be given AN+AD combination for 4 cycles of treatment. This part of the trial will look at whether this combination of drugs is effective and tolerable in participants with Stage I or II cHL with non-bulky mediastinal disease.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Part A: A+AVD
Brentuximab vedotin (A) plus doxorubicin (+A), vinblastine (V), and dacarbazine (D) administered by intravenous (IV) infusion in participants with advanced stage classical Hodgkin lymphoma (cHL) during each treatment cycle.
干预措施: brentuximab vedotin (Drug)
Part A: A+AVD
Brentuximab vedotin (A) plus doxorubicin (+A), vinblastine (V), and dacarbazine (D) administered by intravenous (IV) infusion in participants with advanced stage classical Hodgkin lymphoma (cHL) during each treatment cycle.
干预措施: doxorubicin (Drug)
Part A: A+AVD
Brentuximab vedotin (A) plus doxorubicin (+A), vinblastine (V), and dacarbazine (D) administered by intravenous (IV) infusion in participants with advanced stage classical Hodgkin lymphoma (cHL) during each treatment cycle.
干预措施: vinblastine (Drug)
Part A: A+AVD
Brentuximab vedotin (A) plus doxorubicin (+A), vinblastine (V), and dacarbazine (D) administered by intravenous (IV) infusion in participants with advanced stage classical Hodgkin lymphoma (cHL) during each treatment cycle.
干预措施: dacarbazine (Drug)
Part A: A+AVD
Brentuximab vedotin (A) plus doxorubicin (+A), vinblastine (V), and dacarbazine (D) administered by intravenous (IV) infusion in participants with advanced stage classical Hodgkin lymphoma (cHL) during each treatment cycle.
干预措施: G-CSF (Drug)
Part B: AN+AD
Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage II bulky mediastinal disease and Stage III or IV cHL during each treatment cycle.
干预措施: brentuximab vedotin (Drug)
Part B: AN+AD
Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage II bulky mediastinal disease and Stage III or IV cHL during each treatment cycle.
干预措施: doxorubicin (Drug)
Part B: AN+AD
Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage II bulky mediastinal disease and Stage III or IV cHL during each treatment cycle.
干预措施: dacarbazine (Drug)
Part B: AN+AD
Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage II bulky mediastinal disease and Stage III or IV cHL during each treatment cycle.
干预措施: nivolumab (Drug)
Part C: AN+AD
Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage I or II cHL with non-bulky mediastinal disease during each treatment cycle.
干预措施: brentuximab vedotin (Drug)
Part C: AN+AD
Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage I or II cHL with non-bulky mediastinal disease during each treatment cycle.
干预措施: doxorubicin (Drug)
Part C: AN+AD
Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage I or II cHL with non-bulky mediastinal disease during each treatment cycle.
干预措施: dacarbazine (Drug)
Part C: AN+AD
Brentuximab vedotin (A) plus nivolumab (N), doxorubicin (+A), and dacarbazine (D) administered separately by IV infusion in participants with Stage I or II cHL with non-bulky mediastinal disease during each treatment cycle.
干预措施: nivolumab (Drug)
结局指标
主要结局
Febrile Neutropenia (FN) Rate (Part A)
时间窗: 7.5 months
The FN rate is defined as the number of participants who experience treatment-emergent FN.
Complete Response (CR) Rate at EOT (Parts B and C)
时间窗: 7.8 months
CR rate at EOT is defined as the percentage of participants with CR at EOT, according to the Lugano Classification Revised Staging System for malignant lymphoma (Cheson 2014) with the incorporation of Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) (Cheson 2016), in participants with previously untreated cHL.
次要结局
- Number of Participants With Adverse Events of Clinical Interest (AECI) (Part A)(Approximately up to 7.5 months)
- Primary Refractory Disease Rate (Part A)(10.2 months)
- Complete Response Rate (Part A)(7.2 months)
- Physician-reported Progression Free Survival (PFS) (Part A)(24 months)
- Number of Participants With Subsequent Anticancer Therapy Utilization (Part A)(33.8 months)
- Actual Dose Intensity: Brentuximab Vedotin (Part A)(6.5 months)
- Actual Dose Intensity: Doxorubicin, Vinblastine, Dacarbazine (Part A)(6.5 months)
- Relative Dose Intensity (Part A)(6.5 months)
- Rate of Dose Reduction and Delays: Brentuximab Vedotin (Part A)(6.5 months)
- Rate of Dose Reduction and Delays: Doxorubicin (Part A)(6.5 months)
- Rate of Dose Reduction and Delays: Vinblastine (Part A)(6.5 months)
- Rate of Dose Reduction and Delays: Dacarbazine (Part A)(6.5 months)
- Incidence of Adverse Events (Parts B and C)(8.9 months)
- Incidence of Laboratory Abnormalities (Parts B and C)(8.9 months)
- Overall Response Rate (ORR) at EOT (Parts B and C)(Up to 7.8 months)
- Duration of Response (DOR) at End of Study (Parts B and C)(Up to 51.1 months)
- Duration of Complete Response (DOCR) (Parts B and C)(Up to 51.1 months)
- Event Free Survival (EFS) Rate (Parts B and C)(Months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42)
- PFS Rate (Parts B and C)(At months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42 from the start of study treatment)
- Overall Survival (OS) Rate (Parts B and C)(At months 3, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 39 and 42 from the start of study treatment)