Phase II Study of Brentuximab Vedotin in Combination With Bendamustine and Rituximab, in Patients With CD30 Positive, Relapsed or Refractory B Cell Non-Hodgkin Lymphoma (NHL)
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- CR rate
研究概览
简要总结
This phase II trial studies how well brentuximab vedotin, bendamustine, and rituximab work in treating patients with B-cell non-Hodgkin lymphoma that has returned after a period of improvement or has not responded to previous treatment. Monoclonal antibody-drug conjugates, such as brentuximab vedotin, use antibody to target chemotherapy in cancer cells. Drugs used in chemotherapy, such as bendamustine, work in different ways to kill cancer cells. Monoclonal antibodies, such as rituximab, kill the cancer cells directly, but also harness the immune system to kill the cancer cells. Adding brentuximab to rituximab may improve response rates in CD30 positive, CD20 positive Relapsed Refactory NHL.
详细描述
PRIMARY OBJECTIVES:
I. Complete response (CR) rate and overall response rate (ORR) for patients with relapsed aggressive high-risk non-Hodgkin lymphoma (NHL) treated with brentuximab vedotin, bendamustine and rituximab (S-BR).
SECONDARY OBJECTIVES:
I. To estimate 2-year progression-free survival (PFS). II. To evaluate rate of positron emission tomography (PET)-CR and correlation to 2 year PFS.
III. To evaluate the toxicity of six cycles of S-BR. IV. To evaluate mobilization, stem cell collection, engraftment in patients that proceed to salvage autologous stem cell transplant (ASCT).
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •CD30 detectable B lineage relapsed refractory NHL including the following histologies:
- •Aggressive lymphomas: diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, grey zone lymphomas, high grade B cell lymphomas, and transformed indolent lymphomas
- •Indolent lymphoma: follicular lymphoma, marginal zone lymphoma, small lymphocytic lymphoma; indolent lymphoma patients eligible for this trial should have high tumor burden and high risk disease, as defined by:
- •The Groupe d'Etude des Lymphomes Folliculaires (GELF) criteria
- •Intermediate or high risk by Follicular Lymphoma International Prognostic Index (FLIPI) score or elevated lactose dehydrogenase (LDH)/ beta-2 microglobulin (B2M)
- •Subjects between 18 and 75 years old. Subjects older than 75 years old to be discussed with PI prior to subject consent; consensus between PI and treating physician is required.
- •Karnofsky performance status (KPS) >= 70%, Eastern Cooperative Oncology Group (ECOG) =< 2
- •At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
- •Patients must have received at least one but no more than 4 prior lines of systemic therapy
- •American Heart Association (AHA) class 1 without significant limitation of physical activity
- •Ejection fraction (EF) of at least >= 40% by multigated acquisition (MUGA) or echocardiography (ECHO)
- •Total bilirubin =< 1.5 mg/dl
- •Alanine aminotransferase (ALT), aspartate aminotransferase (AST) less than 2.5 times the upper limit of normal without evidence of active infectious hepatitis
- •Creatinine clearance >= 40 ml/min
- •Platelets > 75,000 cells/ul
- •Absolute neutrophil count (ANC) > 1,000 cells/ul
- •Ability to provide informed consent
- •Females of childbearing potential must have a negative serum or urine beta-human chorionic gonadotropin (HCG) pregnancy test at screening; pregnancy testing is not required for: (a) women who have been post-menopausal for at least 2 years without menses; or (b) women who are surgically sterile (e.g. by means of hysterectomy, tubal ligation, etc.)
- •Males and females of childbearing potential must be able and willing to use an effective contraceptive method during treatment and for three months after completing treatment
排除标准
- •Active infections (bacterial, fungal, or viral)
- •Evidence of sanctuary site involvement by disease, e.g., central nervous system, ocular, testicular involvement
- •Evidence of second malignancy, abnormal cytogenetics, or morphologic evidence of myelodysplastic syndromes (MDS)
- •Recent chemotherapy within 3 weeks of screening
- •Major surgery within 4 weeks of screening
- •Diagnosed or treated for malignancy other than NHL for which patient will be treated, except: malignancy treated with curative intent and with no known active disease present for >= 3 years before subject registration; adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease; adequately treated carcinoma in situ without evidence of disease
- •History of stroke or intracranial hemorrhage within 6 months prior to registration
- •Requires anticoagulation with warfarin or equivalent vitamin K antagonists
- •Requires treatment with strong cytochrome (CYP3A4/5) inhibitors
- •Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any class 3 (moderate) or class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
- •Known history of human immunodeficiency virus or active hepatitis C virus or active hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous antibiotics
- •Women who are pregnant or breastfeeding
- •Prior use of brentuximab vedotin
- •Prior use of bendamustine for indolent lymphoma allowed if > 2 years, CR to bendamustine and well tolerated with no residual > grade 1 toxicity; no prior use of bendamustine for aggressive lymphoma allowed
- •Prior allogeneic transplant
- •Patients with Child-Pugh B or C hepatic impairment
研究组 & 干预措施
Brentuximab, Bendamustine, Rituximab
Brentuximab Vedotin in Combination with Bendamustine and Rituximab
干预措施: Brentuximab (Drug)
Brentuximab, Bendamustine, Rituximab
Brentuximab Vedotin in Combination with Bendamustine and Rituximab
干预措施: Bendamustine (Drug)
Brentuximab, Bendamustine, Rituximab
Brentuximab Vedotin in Combination with Bendamustine and Rituximab
干预措施: Rituximab (Drug)
结局指标
主要结局
CR rate
时间窗: Up to 2 years after completion of study treatment
The complete response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.
Percentage of patients obtaining a CR + PR using Cheson criteria
时间窗: Up to 2 years after completion of study treatment
The overall response rate will be estimated as the proportion of patients with response, with a 95% exact confidence interval.
次要结局
- Median time to progression(At 2 years)
- PFS(At 2 years)
- Complete response rate assessed by PET/CT(Up to 2 years after the completion of study treatment)
- Frequency of adverse events (AEs) and serious AEs assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0(Up to 2 years after completion of study treatment)
- CD34+ peripheral blood stem cells assessed by flow cytometry(Up to 2 years after completion of study treatment)
- Median time to engraftment(Up to 2 years after completion of study treatment)
- Soluble CD30 levels in blood by biochemical assay(48-72 hours after brentuximab vedotin treatment)