A Randomized, Open-Label, Phase 3 Trial of Brentuximab Vedotin(SGN-35) Versus Physician's Choice (Methotrexate or Bexarotene) in Patients With CD30-Positive Cutaneous T-Cell Lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 131
- 主要终点
- Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4)
研究概览
简要总结
The purpose of this study is to determine objective response rate (ORR), lasting at least 4 months (ORR4), with brentuximab vedotin in participants with cluster of differentiation antigen 30 positive (CD30+) cutaneous T-cell lymphoma [mycosis fungoides (MF) and primary cutaneous anaplastic large cell lymphoma (pcALCL) ]compared to that achieved with therapy in the control arm.
详细描述
The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat people who have CD30+ cutaneous T-cell lymphoma (mycosis fungoides and primary cutaneous anaplastic large cell lymphoma). This study will look at the overall response of people who took brentuximab vedotin compared to people who took methotrexate or bexarotene as standard care.
The study enrolled 131 patients. Participants will be randomly assigned (by chance, like flipping a coin) to one of the two treatment groups-which will remain undisclosed to the participant and study doctor during the study (unless there is an urgent medical need):
- Methotrexate 5 to 50 mg or Bexarotene 300 mg/m^2 (as per physician's choice)
- Brentuximab vedotin 1.8 mg/kg
This multicenter trial is being conducted worldwide. The overall time to participate in this study is approximately 6 years. Participants will make multiple visits to the clinic every 12 weeks for a minimum of 24 months after the end of treatment (EOT) visit, and then every 6 months until death, study closure, or 6 years after enrollment of the last participant.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary consent form
- •Male or female participants 18 years or older with diagnosis of mycosis fungoides (MF) or primary cutaneous anaplastic large cell lymphoma (pcALCL)
- •Participants with pcALCL who have received prior radiation therapy or at least 1 prior systemic therapy; participants with MF who have received at least 1 prior systemic therapy
- •Histologically confirmed CD30+ disease by central laboratory assessment and pathology review
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Female participants who are post menopausal, surgically sterile, or agree to practice 2 effective methods of contraception or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant
- •Male participants who agree to practice effective barrier contraception or agree to practice true abstinence, when this is in line with the preferred and usual lifestyle of the participant
- •Clinical laboratory values as specified in protocol
- •A 3-week washout period is required from previous treatments (with the exception of a 12-week washout for antibody-directed or immunoglobulin-based immune therapy, or other monoclonal antibody therapies), unless it is not in the best interest of the patient in the opinion of the investigator. Individual cases should be discussed with the project clinician before enrollment.
排除标准
- •A concurrent diagnosis of systemic ALCL, or other non Hodgkin lymphoma (excluding LyP) or Sezary syndrome or B2 disease
- •Participants with cardiovascular conditions specified in protocols
- •Participants with history of another primary malignancy not in remission for at least 3 years
- •Known active cerebral/meningeal disease, including signs or symptoms of progressive multifocal leukoencephalopathy (PML);
- •Known human immunodeficiency virus (HIV) infection, hepatitis B or Hepatitis C infection
- •Oral retinoid therapy for any indication within 3 weeks of study entry
- •Corticosteroid therapy within 3 weeks or immunosuppressive chemotherapy or any antibody-directed or immunoglobulin-based immune therapy (e.g., immunoglobulin replacement, other monoclonal antibody therapies) within 12 weeks of first dose of study drug
- •Female participants who are lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 of any cycle
- •Previous receipt of brentuximab vedotin Please note that there are additional inclusion and exclusion criteria. The study center will determine if you meet all of the criteria.
- •Site personnel will explain the trial in detail and answer any question you may have if you do qualify for the study. You can then decide whether or not you wish to participate. If you do not qualify for the trial, site personnel will explain the reasons.
研究组 & 干预措施
Brentuximab vedotin
Brentuximab vedotin 1.8 mg/kg, intravenous over approximately 30 minutes, once on Day 1 of each 21-day cycle and may continue as monotherapy for up to a total of 16 cycles (48 weeks).
干预措施: Brentuximab Vedotin (Drug)
Methotrexate or Bexarotene
Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
干预措施: Methotrexate (Drug)
Methotrexate or Bexarotene
Methotrexate 5 to 50 mg, tablets, orally, once weekly (dose adjustment is guided by patient response and toxicity) or Bexarotene 300 mg/m^2, tablets, orally, once daily with meals for up to 48 weeks.
干预措施: Bexarotene (Drug)
结局指标
主要结局
Percentage of Participants Achieving an Objective Response That Lasts at Least 4 Months (ORR4)
时间窗: Each Cycle until disease progression, death End of treatment (Median overall follow-up 38.8 months)
ORR4 was determined by an Independent Review Facility (IRF) based on Global Response Score (GRS) which consisted of a skin assessment by the investigator using the modified severity-weighted assessment tool (mSWAT), nodal and visceral radiographic assessment by an IRF and for the participants with mycosis fungoides (MF) only, detection of circulation Sezary cells. Participants whose first response occurred after the start of subsequent anticancer therapy were excluded. Response Criteria was based on International Society for Cutaneous Lymphomas (ISCL), United States Cutaneous Lymphoma Consortium (USCLC) and Cutaneous Lymphoma Task Force (CLTF) of the European Organisation for Research and Treatment of Cancer (EORTC) Consensus guidelines (Olsen, 2011).
次要结局
- Percentage of Participants Achieving a CR(Each Cycle until disease progression, death or data cutoff (Median overall follow-up 38.8 months))
- Progression-Free Survival (PFS)(Until disease progression, death or data cutoff (Median PFS follow-up of 38.8 months))
- Ctrough: Observed Concentration at the End of a Dosing Interval for Brentuximab Vedotin(Day 1 pre-dose of Cycles 2 and 4)
- Maximum Change From Baseline in Symptom Domain Score of the Skindex-29 Questionnaire(Baseline up to End of Treatment (Week 52))
- Duration of Response (DOR)(Until disease progression, death or data cutoff (Median follow-up 38.8 months))
- DOR of Skin Response(Until disease progression, death or data cutoff (Median follow-up 38.8 months))
- Event-Free Survival (EFS)(From randomization until disease progression, death or data cutoff (Median follow-up 36.8 months))
- Ctrough: Observed Concentration at the End of a Dosing Interval for MMAE for Brentuximab Vedotin(Day 1 pre-dose of Cycles 2 and 4)
- Cmax: Maximum Observed Concentration for Brentuximab Vedotin(Day 1 pre-dose and 30 minutes after infusion in Cycles 1 and 3)
- Cmax: Maximum Observed Concentration for Monomethyl Auristatin (MMAE) for Brentuximab Vedotin(Day 1 pre-dose and 30 minutes after infusion ended in Cycles 1 and 3)
- Number of Participants With Antitherapeutic Antibodies (ATA) to Brentuximab Vedotin(Baseline up to End of Treatment (Week 52))
- Change From Baseline in Functional Assessment of Cancer Therapy General Questionnaire (FACT-G) Score(Day 1 of Cycles 1, 2, 4, 6, 8, 10, 12, 14, 16, at EOT and during posttreatment (LTFU) - (Median follow-up 38.8 months))
- Change From Baseline in the Skindex-29 Questionnaire Total Score(Day 1 of Cycles 1, 2, 4, 6, 8, 10, 12, 14, 16, at End of Treatment (EOT) and during posttreatment long treatment follow-up (LTFU) - (Median follow-up 38.8 months))
- Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)(First dose of study drug through 30 days after last dose of study drug (Up to 450 days))