Efficacy and Safety of Brentuximab Vedotin in Combination With Tislelizumab for the Treatment of CD30-positive Relapsed/Refractory NK/T-cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 40
- 主要终点
- complete response (CR) rate
研究概览
简要总结
This is a single-arm, open-label, multicenter, phase 2 study designed to evaluate the efficacy and safety of brentuximab vedotin combined with PD-1 inhibitor tislelizumab in Chinese patients with relapsed/refractory CD30+ NK/CL. Brentuximab vedotin will be administered as 1.8 mg/kg IV infusion on Day 1 of each 3-week cycle. PD-1 inhibitor tislelizumab will be administered as 200 mg on Day 1 of each 3-week cycle. Patients will receive maximum of 8 cycles if they do not meet the criteria for removal from the study. Patients will be assessed for overall response using the Revised Response Criteria for Malignant Lymphoma (Lugano 2014). Dedicated computed tomography (CT) scans (neck, chest, abdomen, and pelvis) will be performed at Baseline and at Cycles 2, 4 and 8, and positron emission tomography (PET) scans will be performed at Baseline and at Cycles 4 and 8. No additional PET scanning is required beyond Cycle 8 unless clinically indicated (for example, suspected of disease progression). The disease symptoms will be assessed at Baseline and on Day 1 of each cycle. Patients may continue study treatment until the sooner of disease progression, unacceptable toxicity, or completion of 8 cycles. Patients who discontinue study treatment for any reason other than withdrawal of consent will have safety follow-up assessments through 30 days after the last dose of 、study drug (end of treatment [EOT]). Patients who discontinue study treatment with stable disease (SD), responses and progression disease (PD) will be followed for 1-year PFS rate and 1-year OS rate. The CT scan, PET-CT and laboratory examination will be followed based on clinical practice. The study will be closed when all patients enrolled have completed the required follow-up.Toxicity will be evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0 Laboratory values, vital signs, and electrocardiograms (ECGs) will be obtained to evaluate the safety and tolerability of study treatment.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged 18~75 years
- •Histopathology and immunohistochemistry confirmed diagnosis of NK/T-cell lymphoma according to WHO 2016 criteria
- •≥10% CD30 positive for tumor tissue immunohistochemistry
- •Previously treated with asparaginase-based regimens (refractory or relapsed after initial remission)
- •PET/CT or CT/MRI with at least one objectively measurable or evaluable lesion
- •ECOG Performance score 0-2
- •The laboratory test within 1 week before enrollment meets the following conditions:
- •Blood routine: absolute neutrophil count≥1,500/uL, Leukocytes≥3,000/mm3, Hb>8.0g/dL, PLT>100 ×10*9/L. Liver function: ALT, AST≤ 2.5 times the upper limit of normal, TBIL ≤1.5 times the upper limit of normal. Renal function: Cr >2.0 mg/dL and/or creatinine clearance or calculated creatinine clearance > 40 mL/minute , Amylase and/or lipase ≤1.5 x ULN, Coagulation : plasma fibrinogen ≥ 1.0g/L. Cardiac function: LVEF≥50%, ECG does not suggest any acute myocardial infarction, arrhythmia or atrioventricular conduction above I Blocking,
- •Sign the informed consent form,
- •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 informed consent through six months after the last dose of study drug
- •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 during entire study treatment period and through 6 months after the last dose of study drug,
- •Voluntary compliance with research protocols, follow-up plans, laboratory and auxiliary examinations.
排除标准
- •Serious active infection requiring ICU treatment.
- •Patients with any active viral, bacterial, or fungal infections that require intravenous antibiotics within 2 weeks before the first dose of the study drug
- •Known HIV infection or active infection with HBV, HCV. Patients who are infected with HBV but not active hepatitis at the same time are not excluded.
- •Serious complications such as fulminant DIC.
- •Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin.
- •Peripheral neuropathy ≥ Grade 2 (NCI-CTCAE version 5.0 ).
- •Symptomatic neurologic disease compromising normal activities of daily living or requiring medications
- •Known cerebral or meningeal disease (HL or any other etiology), including signs or symptoms of PML
- •Significant organ dysfunction: such as respiratory failure, NYHA classification Class III or IV, chronic congestive heart failure, decompensation Hepatic or renal insufficiency, high blood pressure and diabetes that cannot be controlled despite active treatment, and cerebral vascular thrombosis or hemorrhagic time within the past 6 months.
- •Pregnant and lactating women.
- •Had a history of autoimmune diseases, and disease was active in the last 6 months, and was still taking oral immunosuppressant in the past three months, with daily prednisone dose greater than 10 mg
- •Patients who are known to be seriously allergic to any of the drugs in the study regimen (e.g. life-threatening allergic symptoms such as anaphylactic shock).
- •Patients combined with other tumors who require surgery or chemotherapy within 6 months.
- •Other experimental drugs are being used.
- •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
CD30-positive Relapsed/Refractory NK/T-cell Lymphoma
Brentuximab vedotin will be administered as 1.8 mg/kg IV infusion on Day 1 of each 3-week cycle. PD-1 inhibitor tislelizumab will be administered as 200 mg on Day 1 of each 3-week cycle. Patients will receive maximum of 8 cycles if they do not meet the criteria for removal from the study. Patients will be assessed for overall response using the Revised Response Criteria for Malignant Lymphoma (Lugano 2014). Dedicated computed tomography (CT) scans (neck, chest, abdomen, and pelvis) will be performed at Baseline and at Cycles 2, 4 and 8, and positron emission tomography (PET) scans will be performed at Baseline and at Cycles 4 and 8.
干预措施: Brentuximab Vedotin in Combination with Tislelizumab (Drug)
结局指标
主要结局
complete response (CR) rate
时间窗: 1 year after treatment completion
complete response (CR) rate, evaluated by PET-CT and CT/MRI, according to Lugano 2014 criteria
次要结局
- 1-year overall survival rate (OS)(1 year after treatment completion)
- overall response rate (ORR)(1 year after treatment completion)
- 1-year progression free survival rate (PFS)(1 year after treatment completion)
- adverse events according to CTCAE 5.0(1 year after treatment completion)
- disease control rate (DCR)(1 year after treatment completion)
研究者
Peng Liu
Chief of hematology department
Shanghai Zhongshan Hospital