A Phase 2, Single-Arm, Open-label Study of Brentuximab Vedotin in Chinese Patients With Relapsed/Refractory CD30-Positive Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 39
- 试验地点
- 7
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy, safety and pharmacokinetics (PK) of brentuximab vedotin as a single agent in Chinese participants with relapsed/refractory CD30+ Hodgkin Lymphoma (HL) or Systemic Anaplastic Large Cell Lymphoma (sALCL).
详细描述
The drug being tested in this study is called brentuximab vedotin. This study will look at efficacy, safety and PK of brentuximab vedotin in Chinese participants with relapsed/refractory CD30+ HL or sALCL.
The study will enroll approximately 30 patients. Participants will receive:
• Brentuximab vedotin 1.8 mg/kg
All participants will be administered IV infusion on Day 1 each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles.
This multi-center trial will be conducted in China only. The overall time to participate in this study is 3.5 years. Participants will make multiple visits to the clinic, and will be followed for overall survival (OS) every 12 weeks until death, withdrawal of consent, 18 months after end of treatment (EOT) or study closure, whichever occurs first.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have histologically confirmed CD30+ hodgkin lymphoma (HL) or systemic anaplastic large cell lymphoma (sALCL). Immunohistochemistry or flow cytometry may be performed on either original diagnostic biopsy material or biopsy of relapsed disease, and pathology reports of CD30+ or their copies should be retained at the site.
- •With CD30+ HL or sALCL who have relapsed from or are refractory to previous treatments.
- •Fluorodeoxyglucose (FDG)- positron emission tomography (PET) positive and measurable disease of at least 1.5 cm in the longest diameter by computed tomography (CT), as assessed by the site.
- •Must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or
- •Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) sampling.
- •Must have the following required screening laboratory data. Participants must not have received recombinant granulocyte-colony stimulating factor (G-CSF) or platelet transfusion within 1 week before the screening hematology assessment.
- •Absolute neutrophil count ≥1500/μL.
- •Platelet count ≥75,000/μL.
- •Serum bilirubin level ≤1.5 times the upper limit of the normal range (ULN).
- •Serum creatinine level ≤1.5 times the ULN.
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5 times the ULN.
- •Survival for 3 or more months must be expected.
排除标准
- •With current diagnosis of primary cutaneous anaplastic large cell lymphoma (ALCL) (participants with other organ involvement who have transformed to sALCL are eligible).
- •With any active viral, bacterial, or fungal infection within 2 weeks before the first dose of brentuximab vedotin.
- •With cardiac failure categorized as Class III or IV according to the New York Heart Association criteria, uncontrolled coronary artery disease or uncontrolled arrhythmia despite of appropriate medical therapy, or a history of myocardial infarction within 6 months before the first dose of brentuximab vedotin.
- •With uncontrolled diabetes mellitus.
- •Peripheral neuropathy ≥Grade
- •With a history of another malignancy that has not been in remission for at least 3 years. The following are exempt from the 3-year limit:
- •Nonmelanoma skin cancer.
- •Curatively treated localized prostate cancer.
- •Cervical carcinoma in situ.
- •With known cerebral/meningeal disease (HL or any other etiology), including signs or symptoms of progressive multifocal leukoencephalopathy (PML).
- •With a positive result in the screening test for human immunodeficiency virus (HIV) antibody.
- •Known hepatitis B virus (HBV) surface antigen seropositive or positive hepatitis C virus (HCV) antibody. Note: participants who have positive HBV core antibody can be enrolled but must have an undetectable HBV viral load.
- •With a history of liver fibrosis or cirrhosis and clinical signs and symptoms indicating liver fibrosis or cirrhosis.
- •Have received autologous stem cell transplantation (auto-SCT) within 12 weeks before the first dose of brentuximab vedotin.
- •With history of allogeneic stem cell transplantation (allo-SCT).
- •Have received treatment for malignancies (including radiation, chemotherapy, and hormone therapy) within 4 weeks before the first dose of brentuximab vedotin and participants who have received treatment for malignancies with biologics (including molecular target drug) or radioisotopic therapy within 12 weeks before the first dose of brentuximab vedotin.
- •Have unresolved toxicity higher than Grade 1 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] version 4.03) attributed to any prior therapy/procedure (excluding alopecia or non-clinically significant and asymptomatic laboratory abnormalities).
- •Have received systemic corticosteroids at doses greater than the equivalent of 20 mg/day of prednisone within 1 week before the first dose of brentuximab vedotin.
- •Comorbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the participant inappropriate for entry into this study or interfere significantly with the proper assessment of the safety and toxicity of the prescribed regimens.
研究组 & 干预措施
Brentuximab Vedotin 1.8 mg/kg
Brentuximab vedotin 1.8 mg/kg, intravenous (IV) infusion on Day 1 of each 3-week cycle until the sooner of disease progression, unacceptable toxicity, or completion of 16 cycles.
干预措施: Brentuximab Vedotin (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)
An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (eg, a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a drug, whether or not it is considered related to the drug. A treatment-emergent adverse event (TEAE) is defined as an adverse event with an onset that occurs or worsens after receiving study drug.
Number of Participants With Abnormal Vital Signs Reported as Adverse Events
时间窗: First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)
Vital signs included blood pressure in the sitting position, pulse rate, axillary temperature and weight. Abnormal vital sign values considered by the investigator to be clinically significant were recorded as Adverse Events.
Overall Response Rate (ORR)
时间窗: Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment until disease progression death or end of treatment (approximately 12 months)
ORR is defined as the percentage of participants who have achieved complete remission (CR)=disappearance of all evidence of disease or partial remission (PR)=regression of greater than or equal to 50% of measurable disease and no new site by end of treatment (EOT) per Cheson 2007 Revised Response Criteria for Malignant Lymphoma.
Number of Participants With Abnormal Clinical Laboratory Findings Reported as Adverse Events
时间窗: First dose of study drug up to 30 days after last dose of study drug (approximately 12 months)
Clinical Laboratory tests included tests of Chemistry, Hematology and Urinalysis prespecified in the protocol. Abnormal laboratory values assessed by the investigator that lead to discontinuation or delay in treatment, dose modification, therapeutic intervention, or were considered by the investigator to be clinically significant changes from Baseline were recorded as Adverse Events. Neutropenia (pooled) includes preferred terms Neutropenia and Neutrophil count decreased.
次要结局
- Complete Remission (CR) Rate(Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment, and every 12 weeks during PFS follow-up period, until disease progression death or end of treatment (approximately 12 months))
- Duration of Response (DOR)(Up to 3.2 years)
- Progression Free Survival (PFS)(Up to 3.2 years)
- Overall Survival (OS)(Up to 3.2 years)
- B Symptom Resolution Rate(Day 1 of each cycle (each cycle was of 3 weeks) up to 30 days after last dose of study drug (approximately 12 months))
- Cmax: Maximum Observed Serum Concentration for Total Antibody (TAb)(Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose)
- AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for Brentuximab Vedotin ADC(Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose)
- AUC(0-∞): Area Under the Serum Concentration-time Curve From Time 0 to Infinity for TAb(Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose)
- Cmax: Maximum Observed Serum Concentration for Brentuximab Vedotin Antibody-drug Conjugate (ADC)(Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose)
- Cmax: Maximum Observed Plasma Concentration for Monomethyl Auristatin E (MMAE)(Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose)
- Tmax: Time to Reach the Maximum Serum Concentration (Cmax) for TAb(Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose)
- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for MMAE(Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose)
- AUC(0-∞): Area Under the Plasma Concentration-time Curve From Time 0 to Infinity for MMAE(Cycle (each cycle was of 3 weeks) 1: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose)
- Number of Participants With Antitherapeutic Antibodies (ATA) and Neutralizing Antitherapeutic Antibodies (nATA) to Brentuximab Vedotin(Baseline, at Cycles (each cycle was of 3 weeks) 2, 4, 7, 10, 13, and 16 during treatment until disease progression, death or end of treatment (approximately 12 months))
- Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for Brentuximab Vedotin ADC(Cycles (each cycle was of 3 weeks) 1 and 2: Day 1 pre-dose and at multiple time points (up to 336 hours) post-dose)