A Randomized Phase IIb Study, Evaluating Efficacy of Salvage Therapy With Brentuximab Vedotin-ESHAP vs ESHAP in Patients With Relapsed / Refractory Classical Hodgkin's Lymphoma, Followed by Brentuximab Vedotin Consolidation (Instead of Autologous Hematopoietic Stem Cell Transplantation) in Those Who Attained a Metabolic Complete Remission After Salvage Therapy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 150
- 试验地点
- 19
- 主要终点
- PET-CT result
研究概览
简要总结
A Randomized Phase IIb Study, Evaluating Efficacy of Salvage Therapy with Brentuximab Vedotin-ESHAP vs ESHAP in Patients with Relapsed / Refractory Classical Hodgkin's Lymphoma, Followed by Brentuximab Vedotin Consolidation (instead of Autologous Hematopoietic Stem Cell Transplantation) in Those who Attained a Metabolic Complete Remission after Salvage Therapy
详细描述
A phase IIb open label multi-center trial in patients with refractory / relapsed cHL.
Patients are randomized (1:1) to receive:
• ESHAP- BV (Etoposide [40 mg/m2/ day IV, D1-4], Solumedrol [250 mg/day IV, D1-4], high dose Ara-C [2 g/m2 IV, D5] and cisplatinum [25 mg/m2/day IV, D1-4] + BV [1.8 mg/kg IV, D1], every 21 days (3 cycles, q21 days).
Or
• ESHAP (Etoposide [40 mg/m2/ day IV, D1-4], Solumedrol [250 mg/day IV, D1-4], high dose Ara-C [2 g/m2 IV, D5] and cisplatinum [25 mg/m2/day IV, D1-4] (3 cycles, q21 days)
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with classical HL CD30+ confirmed histologically (either at the time of diagnosis / at the time of first relapse) will be included in the trial
- •Male or female patients 18 to 65 years of age
- •Voluntary written informed consent must be given before performance of any study-related procedure not part of standard medical care, with the understanding that consent may be withdrawn by the patient at any time without prejudice to future medical care
- •Female patient is either post-menopausal for at least 1 year before the screening visit or surgically sterile or if of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse
- •Male patients, even if surgically sterilized, (i.e., status post-vasectomy) agree to practice effective barrier contraception during the entire study period and through 6 months after the last dose of study drug, or agrees to completely abstain from heterosexual intercourse
- •ECOG 0 to 2
- •Measurable disease at time of enrolment (lymphadenopathy/ extranodal mass of at least 1.5 cm)
- •No evidence of neuropathy grade ≥2
- •Clinical laboratory values as specified in the protocol below within 7 days before the first dose of study drug
排除标准
- •Lymphocyte predominant nodular Hodgkin's lymphoma
- •Prior treatment with brentuximab vedotin
- •Female patient who are both lactating and breast-feeding or have a positive serum pregnancy test during the screening period or a positive pregnancy test on Day 1 before first dose of study drug
- •Any serious medical or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to the protocol.
- •Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML)
- •Symptomatic neurologic disease compromising normal activities of daily living or requiring medic
- •Any sensory or motor peripheral neuropathy greater than or equal to Grade 2
- •Known history of any of the following cardiovascular conditions defined in the protocol
- •Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose
- •Patients that have not completed any prior treatment chemotherapy and/or other investigational agents within at least 5 half-lives (or 28 days if the half-lives are unknown) of last dose of that prior treatment
- •Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin.
- •Known human immunodeficiency virus (HIV) positive
- •Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection
- •Focal radiation therapy within 30 days prior to study recruitment
- •Major surgery within 28 days prior to randomization
- •Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have evidence of residual disease.
- •Patients with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
研究组 & 干预措施
Induction ESHAP
3 Cycles ESHAP ( 21 days) : Etoposide [40 mg/m2/ day IV, D1-4], Solumedrol [250 mg/day IV, D1-4], High dose Ara-C [2 g/m2 IV, D5] Cisplatinum [25 mg/m2/day IV, D1-4]
干预措施: Induction without Brentuximab Vedotin (Drug)
Induction ESHAP
3 Cycles ESHAP ( 21 days) : Etoposide [40 mg/m2/ day IV, D1-4], Solumedrol [250 mg/day IV, D1-4], High dose Ara-C [2 g/m2 IV, D5] Cisplatinum [25 mg/m2/day IV, D1-4]
干预措施: Consolidation with Brentuximab Vedotin (Drug)
Induction BV-ESHAP
3 Cycles of Brentuximab VEedotin + ESHAP ( 21 days) : Etoposide [40 mg/m2/ day IV, D1-4], Solumedrol [250 mg/day IV, D1-4], High dose Ara-C [2 g/m2 IV, D5] Cisplatinum [25 mg/m2/day IV, D1-4] Brentuximab Vedotin [1.8 mg/kg IV, D1]
干预措施: Induction with Brentuximab vedotin (BV) (Drug)
Induction BV-ESHAP
3 Cycles of Brentuximab VEedotin + ESHAP ( 21 days) : Etoposide [40 mg/m2/ day IV, D1-4], Solumedrol [250 mg/day IV, D1-4], High dose Ara-C [2 g/m2 IV, D5] Cisplatinum [25 mg/m2/day IV, D1-4] Brentuximab Vedotin [1.8 mg/kg IV, D1]
干预措施: Consolidation with Brentuximab Vedotin (Drug)
结局指标
主要结局
PET-CT result
时间窗: 4-6 weeks after the Cycle 3 started (each cycle is 21 days)
PET-CT negative, Deauville scores 1 and 2
次要结局
- Duration of response (DOR)(At the end of two years of last dose of consoldation Brentuximab VEdotin treatment)
- progression-free survival (PFS)(At the end of two years of last dose of consoldation Brentuximab VEdotin treatment)
- Duration of response(At the end of two years of last dose of consoldation Brentuximab VEdotin treatment)
- Overall Survival (OS)(At the end of two years of last dose of consoldation Brentuximab VEdotin treatment)