Brentuximab Vedotin Associated With Chemotherapy in Untreated Patients With Stage I/II Unfavourable Hodgkin Lymphoma. A Randomized Phase II LYSA-FIL-EORTC Intergroup Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 170
- 试验地点
- 65
- 主要终点
- PET2 assessment
研究概览
简要总结
This study aims to evaluate the efficacy of brentuximab vedotin + AVD combination (doxorubicine, vinblastine, dacarbazine) in patients with Hodgkin lymphoma stage I / II with an unfavorable diagnosis, assessed by the negativity of PET (positron emission tomography ) after two cycles of chemotherapy.
详细描述
Patients will receive either ABVD chemotherapy (standard treatment = doxorubicin, bleomycin, vinblastine, dacarbazine) or the Brentuximab vedotin in combination with chemotherapy AVD (study treatment), depending on randomization. Radiotherapy is planned after chemotherapy or immunochemotherapy.
PET scans will be performed before inclusion, after 2 cycles of chemotherapy and after 4 cycles of chemotherapy (if PET after two cycles was positive), at the end of treatment and during follow-up period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Histologically confirmed CD30+ classical Hodgkin lymphoma
- •Supradiaphragmatic Ann Arbor clinical stage I or II
- •Previously untreated
- •PET scan without IV contrast at diagnosis available for central review with at least one hypermetabolic lesion
- •Unfavourable (U) characteristics according to the classic EORTC/LYSA clinical prognostic factors, including patients with at least one of the following factors:
- •CSII ≥ 4 nodal areas
- •age ≥ 50 yrs
- •M/T ratio ≥ 0.35
- •ESR ≥ 50 (without B-symptoms) or ESR ≥ 30 with B-symptoms
- •ECOG performance status 0-2
- •Life expectancy > 6 months
- •Age 18 to 60 years
- •Availability for periodic blood sampling, study-related assessments, and management of toxicity at the treating institution.
- •Female patients who:
- •Are postmenopausal for at least 1 year before the screening visit, OR are surgically sterile, OR
- •If they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, through 6 months after the last dose of study drug, OR agree to completely abstain from heterosexual intercourse
- •Male patients, even if surgically sterilized (ie, status postvasectomy), who:
- •o Agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
- •Written informed consent.
- •Required baseline laboratory data:
- •Absolute neutrophil count ≥ 1,500/µL
- •Platelet count ≥ 75,000/ µL
- •Hemoglobin ≥ 8g/dL
- •Serum total bilirubin ≤ 1.5 X ULN unless the elevation is known to be due to Gilbert syndrome.
- •Serum creatinine ≤ 2.0 mg/dL and/or calculated creatinine clearance > 40 mL/minute (Cockcroft-Gault formula or MDRD)
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 X ULN
排除标准
- •Histological diagnosis different from classical Hodgkin Lymphoma. Nodular lymphocyte predominant subtypes (nodular paragranuloma or Poppema paragranuloma) are excluded.
- •Known cerebral or meningeal disease of any etiology, including signs or symptoms of PML
- •Any sensory or motor peripheral neuropathy ≥ Grade 2
- •Known history of any of the following cardiovascular conditions
- •Myocardial infarction within 2 years of randomization
- •New York Heart Association (NYHA) Class III or IV heart failure (see Appendix 14)
- •Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities
- •Recent evidence (within 30 days before first dose of study drug) of a left-ventricular ejection fraction <50%
- •Unstable diabetes mellitus (to avoid uninterpretable FDG-PET scan).
- •Known HIV positive
- •HCV positive
- •HBV positive. This means:
- •HBsAg positive
- •HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral DNA (HBsAg negative patients and viral DNA negative and patients seropositive due to a history of hepatitis B vaccine are eligible).
- •Any history of cancer during the last 5 years, with the exception of non-melanoma skin tumors. Carcinoma in situ of any type not excluded if complete resection.
- •Dementia or altered mental status
- •Pregnancy or breastfeeding.
- •Previous treatment with any anti-CD30 antibody.
- •Known hypersensitivity to any excipients contained in the BV formulation or known contra-indication to any drug contained in the chemotherapy regimens
- •Treatment with corticosteroids before baseline PET scan
- •Known active viral, bacterial, or fungal infection requiring treatment with antimicrobial therapy or with untreated known active Grade 3 viral, bacterial, or fungal infection, within 2 weeks prior to the first dose of BV
- •Treatment with any investigational drug within 30 days before first cycle of treatment
研究组 & 干预措施
ABVD
Patients in standard arm receive Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine on Day 1 and D14 of each 4-week-cycle during 4 cycles
干预措施: Vinblastine (Drug)
ABVD
Patients in standard arm receive Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine on Day 1 and D14 of each 4-week-cycle during 4 cycles
干预措施: Dacarbazine (Drug)
ABVD
Patients in standard arm receive Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine on Day 1 and D14 of each 4-week-cycle during 4 cycles
干预措施: Doxorubicin (Drug)
ABVD
Patients in standard arm receive Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine on Day 1 and D14 of each 4-week-cycle during 4 cycles
干预措施: Bleomycin (Drug)
AVD+BV
Patients in experimental arm receive Doxorubicin, Vinblastine, Dacarbazine and Brentuximab vedotin on Day 1 and D14 of each 4-week-cycle during 4 cycles
干预措施: Doxorubicin (Drug)
AVD+BV
Patients in experimental arm receive Doxorubicin, Vinblastine, Dacarbazine and Brentuximab vedotin on Day 1 and D14 of each 4-week-cycle during 4 cycles
干预措施: Vinblastine (Drug)
AVD+BV
Patients in experimental arm receive Doxorubicin, Vinblastine, Dacarbazine and Brentuximab vedotin on Day 1 and D14 of each 4-week-cycle during 4 cycles
干预措施: Dacarbazine (Drug)
AVD+BV
Patients in experimental arm receive Doxorubicin, Vinblastine, Dacarbazine and Brentuximab vedotin on Day 1 and D14 of each 4-week-cycle during 4 cycles
干预措施: Brentuximab Vedotin (Drug)
结局指标
主要结局
PET2 assessment
时间窗: 8 weeks
Assessment of PET after two cycles according to the five-point scale Deauville criteria (Negative = 1, 2, 3 and Positive = 4, 5), based on central review.
次要结局
- Complete response (CR) rate(16 weeks)
- Progression free survival (PFS)(5 years)
- Overall survival (OS)(5 years)