LCCC 1115: A Pilot Feasibility Trial of Induction Chemotherapy With ABVD Followed by Brentuximab Vedotin (SGN-35) Consolidation in Patients With Previously Untreated Non-Bulky Stage I or II Hodgkin Lymphoma (HL)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 6
- 主要终点
- Percentage of Patients With Positron Emission Tomography (PET) Negative Disease
研究概览
简要总结
The standard chemotherapy for Hodgkin lymphoma is called ABVD which is a combination of 4 chemotherapy drugs (doxorubicin, bleomycin, vinblastine, and dacarbazine). The number of cycles of ABVD chemotherapy Hodgkin lymphoma patients receive is about 4-6 cycles. In addition to the ABVD chemotherapy, patients with Hodgkin lymphoma will routinely receive radiation therapy. The use of chemotherapy and radiation may cause long term treatment related side effects such as heart problems and other cancers. Researchers are trying to find if combining ABVD chemotherapy with new drugs and reducing the number of ABVD chemotherapy cycles given is just as effective as the standard Hodgkin treatment.
Brentuximab vedotin is approved by the United States Food and Drug administration (FDA) for the treatment of Hodgkin lymphoma that has come back (relapsed). For this research study, the use of brentuximab vedotin in newly diagnosed Hodgkin lymphoma is considered investigational. Brentuximab vedotin is an antibody that also has a chemotherapy drug attached to it. Antibodies are proteins that are part of your immune system. They can stick to and attack specific targets on cells. The antibody part of the brentuximab vedotin sticks to a target called cluster of differentiation antigen 30 (CD30). CD30 is an important molecule on some cancer cells and some normal cells of the immune system.
The purpose of this research study is to see the effects of treatment with fewer cycles of the combination chemotherapy, ABVD, followed by the study drug brentuximab vedotin has on study participants and Hodgkins lymphoma.
详细描述
This study is designed as a single arm pilot feasibility trial using an induction of 2-6 cycles of ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) chemotherapy followed by 6 cycles of brentuximab vedotin (SGN-35) consolidation for previously untreated patients with stage I and II non-bulky Hodgkin Lymphoma (HL).
Feasibility will be determined by the percentage of patients who have no clinical evidence of HL, and achieve positron emission tomograph (PET) negative disease post brentuximab consolidation. We anticipate approximately 40 patients will be eligible across participating centers (including UNC, Mayo Clinic, and the UNC Cancer Network (UNCCN)) over a 2 year period. A future phase II study evaluating progression free survival (PFS) after ABVD followed by brentuximab vedotin will be considered feasible if ≥ 13 of 15 patients enrolled in this pilot trial become PET negative after brentuximab vedotin consolidation.
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 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Previously untreated stage I or II non-bulky Hodgkin lymphoma
- •No mediastinal mass >0.33 maximum intrathoracic diameter on chest x-ray (see Appendix B)
- •No adenopathy ≥7.5 cm in its largest diameter
- •Measurable disease as assessed by 2 dimensional measurement by CT (>2cm or 1.5 cm if 0.5 cm slices are used, as in spiral CT scan)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- •Age ≥18 years and ≤60 years of age
- •Life expectancy of at least 3 months
- •Adequate bone marrow function (without transfusion support within one week of screening) as demonstrated by:
- •Hemoglobin ≥ 8 g/dL
- •Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
- •Platelet count ≥ 75,000/mm3
- •Adequate hepatic and renal function as demonstrated by:
- •Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)
- •Total serum bilirubin ≤1.5 x ULN
- •Serum creatinine ≤ 2.0 mg/dL
- •Negative serum human chorionic gonadotropin (β-hCG) pregnancy test within 72 hours of day 1 of treatment with ABVD in women of child-bearing potential
- •Females of childbearing potential, and males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 6 months following the last dose of brentuximab vedotin. Effective contraception is defined as any medically recommended method (or combination of methods) as per standard of care, including abstinence. Females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy.
- •Signed an institutional review board (IRB)-approved informed consent document for this protocol
- •Prior to Day 1 of brentuximab vedotin, patients must again meet the following inclusion criteria:
- •Adequate bone marrow function (without transfusion support within one week of D1 of brentuximab vedotin) as demonstrated by:
- •Hemoglobin ≥ 8 g/dL
- •Absolute neutrophil count (ANC) ≥ 1,000 cells/mm3
- •Platelet count ≥ 75,000/mm3
- •Adequate hepatic and renal function as demonstrated by:
- •Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN)
- •Total serum bilirubin ≤1.5 x ULN
- •Serum creatinine ≤ 2.0 mg/dL
- •Achieved at least a partial response (PR) (and not progressed) after ABVD therapy
排除标准
- •Prior therapies for treatment of HL including involved field radiation therapy or any prior treatment for any malignancy with anthracyclines.
- •Bulky disease (defined as a mass measuring > 7.5 cm or one-third the maximal diameter of the thoracic cavity)
- •Known central nervous system (CNS) involvement
- •Symptomatic pulmonary disease currently requiring regular medication including but not restricted to bronchodilators
- •Known history of human immunodeficiency virus (HIV), hepatitis B and hepatitis C (testing is not necessary if patient does not have history of these diseases, and no risk factors for acquisition of these viruses)
- •Cardiac disease with left ventricular ejection fraction of less than 45%
- •Known hypersensitivity to any excipient contained in the drug formulation of brentuximab vedotin or any component of ABVD
- •Medical or other condition that would represent an inappropriate risk to the patient or would likely compromise achievement of the primary study objective
- •Other active malignancies with the exception of:
- •Non-melanoma skin cancer
- •Cervical carcinoma in situ without evidence of disease
- •Prostatic intraepithelial neoplasia without evidence of prostate cancer
- •Pregnant or lactating women
- •Prior to Day 1 of brentuximab vedotin, please verify the patient does not meet the criteria below:
- •Symptomatic pulmonary disease currently requiring regular medication including but not restricted to bronchodilators
研究组 & 干预措施
ABVD followed by Brentuximab vedotin
Single arm trial
干预措施: Brentuximab vedotin (Drug)
ABVD followed by Brentuximab vedotin
Single arm trial
干预措施: ABVD (Drug)
结局指标
主要结局
Percentage of Patients With Positron Emission Tomography (PET) Negative Disease
时间窗: 12 months
Percentage of patients who convert to PET negative disease post consolidation. This is defined by PET with Deauville \<=2. The Deauville 5-point scoring system is a five-point scoring system for the Fluorodeoxyglucose (FDG) avidity of a Hodgkin's lymphoma or Non-Hodgkin's lymphoma tumor mass as seen on FDG Positron emission tomography: Score 1: No uptake above the background Score 2: Uptake ≤ mediastinum Score 3: Uptake \> mediastinum but ≤ liver Score 4: Uptake moderately increased compared to the liver at any site Score 5: Uptake markedly increased compared to the liver at any site Score X: New areas of uptake unlikely to be related to lymphoma
次要结局
- Number of Participant Who Achieved a Complete Response(12 months)
- Conversion Rate to Complete Response. Number of Participants Who Had a Partial Response Post ABVD Who Converted to a Complete Response.(12 months)
- 3 Year Progression Free Survival Rate(3 years)
- 3 Year Time to Progression Rate(3 years)
- Number of Adverse Events Attributed to Brentuximab Vedotin With a Grade 3 or Higher(12 months)