Clinical Trial of Brentuximab Vedotin in Classical Hodgkin Lymphoma
关键词
抽象
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.
日期
| 最后验证: | 07/05/2020 |
| 首次提交: | 08/21/2018 |
| 提交的预估入学人数: | 08/21/2018 |
| 首次发布: | 08/23/2018 |
| 上次提交的更新: | 07/05/2020 |
| 最近更新发布: | 07/07/2020 |
| 实际学习开始日期: | 01/27/2019 |
| 预计主要完成日期: | 07/06/2022 |
| 预计完成日期: | 06/06/2026 |
状况或疾病
干预/治疗
Drug: brentuximab vedotin
Drug: doxorubicin
Drug: Part A: A+AVD
Drug: dacarbazine
Drug: Part A: A+AVD
Drug: nivolumab
相
手臂组
| 臂 | 干预/治疗 |
|---|---|
| Experimental: 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. | Drug: Part A: A+AVD 6 mg/m^2 by IV infusion |
| Experimental: 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. | |
| Experimental: 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. |
资格标准
| 有资格学习的年龄 | 12 Years 至 12 Years |
| 有资格学习的性别 | All |
| 接受健康志愿者 | 是 |
| 标准 | Inclusion Criteria - Treatment-naïve, classic Hodgkin lymphoma (cHL) participants - Participants enrolling in Part A of the study must have Ann Arbor Stage III or IV disease - Participants enrolling in Part B of the study must have Ann Arbor Stage II with bulky mediastinal disease, or Stage III or IV - Participants enrolling in Part C of the study must have Ann Arbor Stage I or II with non-bulky mediastinal disease - Histologically confirmed cHL according to the current World Health Organization (WHO) Classification - Bidimensional measurable disease as documented by PET/CT or CT imaging - Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Exclusion Criteria - Nodular lymphocyte predominant HL - History of another malignancy within 3 years of the first dose of study drug or any evidence of residual disease from a previously diagnosed malignancy. Exceptions are malignancies with a negligible risk or metastasis or death. Participants with nonmelanoma skin cancer, localized prostate cancer, or carcinoma in situ of any type are not excluded if they have undergone complete resection - Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy within 12 weeks of the first study drug dose, unless underlying disease has progressed on treatment - Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways - Active cerebral/meningeal disease related to the underlying malignancy - Any active Grade 3 or higher viral, bacterial, or fungal infection within two weeks of the first dose of study drug (Grade 3 defined by the National Cancer Institute's Common Terminology Criteria for Adverse Events, NCI CTCAE Version 4.03) - Current therapy with other systemic anti-neoplastic or investigational agents - Planned consolidative radiotherapy (Parts B and C only) - Active interstitial lung disease that is symptomatic or may interfere with the detection or management of suspected drug-related pulmonary toxicity (Parts B and C only) - Grade 3 or higher pulmonary disease unrelated to underlying malignancy - Idiopathic interstitial pneumonia or diffusing capacity of the lung for carbon monoxide <50% predicted - History of a cerebral vascular event within 6 months of first dose of study drug - Child-Pugh B or C hepatic impairment - Grade 2 or higher peripheral sensory or motor neuropathy - Participants with acute or chronic graft-versus-host-disease (GvHD) or receiving immunosuppressive therapy as treatment or as prophylaxis against GvHD - Previous treatment with brentuximab vedotin - Participants who are pregnant or breastfeeding - Other serious condition that would impair the participant's ability to receive or tolerate the planned treatment and follow-up |
结果
主要结果指标
1. Febrile Neutropenia (FN) Rate (Part A) [Up to 6 months]
2. Complete response (CR) rate (Parts B and C) [Up to 6 months]
次要成果指标
1. Primary Refractory Disease Rate (Part A) [Up to 9 months]
2. CR Rate (Part A) [Up to 6 months]
3. Physician-reported Progression Free Survival (PFS) (Part A) [Up to 2 years]
4. Subsequent Anticancer Therapy Utilization Rate (Part A) [Up to 2.5 years]
5. Mean Dose Intensity (Part A) [Up to 6 months]
6. Rate of Dose Reduction and Delays (Part A) [Up to 6 months]
7. Incidence of adverse events (Parts B and C) [Up to 7 months]
8. Incidence of laboratory abnormalities (Parts B and C) [Up to 7 months]
9. Overall response rate (ORR) at EOT (Parts B and C) [Up to 6 months]
10. Duration of response (DOR) (Parts B and C) [Up to 5 years]
11. Duration of complete response (DOCR) (Parts B and C) [Up to 5 years]
12. Event-free survival (EFS) (Parts B and C) [Up to 5 years]
13. PFS (Parts B and C) [Up to 5 years]
14. Overall survival (OS) (Parts B and C) [Up to 5 years]
