A Phase 2, Single-Arm, Open-Label, Multicenter Study of Brentuximab Vedotin in Combination With Cyclophosphamide, Doxorubicin (Hydroxydaunorubicin), Prednisone (CHP) in the Frontline Treatment of Chinese Patients With CD30-Positive (CD30+) Peripheral T-Cell Lymphomas (PTCL)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 52
- 试验地点
- 19
- 主要终点
- Percentage of Participants With Clinically Significant Vital Signs
研究概览
简要总结
This study will use a combination of Brentuximab vedotin with CHP to treat adult Chinese participants with CD30+ PTCL.
The main aims of the study are to evaluate:
- Side effect from the A+CHP
- Check how much A+CHP stays in their blood over time. This will help Takeda to work out the best dose to give people in the future.
- If A+CHP improves outcome of newly diagnosed CD30+ PTCL
Brentuximab vedotin will be given through vein on Day 1 of each 21-day cycle. Cyclophosphamide and doxorubicin will be given through vein. Prednisone will be given orally daily on Days 1 through 5.
详细描述
The drug being tested in this study is called brentuximab vedotin. Brentuximab vedotin is being tested to treat CD30+ PTCL in Chinese participants. This study will look at the efficacy, safety, and pharmacokinetics (PK) of A+CHP as frontline treatment for newly diagnosed CD30+ PTCL.
The study will enroll approximately 52 participants. Participants will be enrolled in a single group to receive:
• Brentuximab vedotin 1.8 milligrams per kilogram (mg/kg) + Cyclophosphamide 750 milligrams per square meter (mg/m^2), Doxorubicin 50 mg/m^2 and Prednisone 100 mg
This multi-center trial will be conducted in China. The overall time to participate in this study is approximately 36 months.
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
- •Participants must have newly diagnosed CD30+ PTCL, per the Revised European American Lymphoma 2016 World Health Organization (WHO) classification, by local assessment. Tumor specimen must be submitted before enrollment for subsequent central pathology review to confirm histology (and anaplastic lymphoma kinase (ALK) status, if applicable), and CD30 expression. Eligible histologies include:
- •ALK-positive systemic anaplastic large cell lymphoma (sALCL) with an International Prognostic Index (IPI) score of ≥
- •ALK-negative sALCL.
- •PTCL- not otherwise specified (NOS).
- •Angioimmunoblastic T-cell lymphoma (AITL).
- •Enteropathy associated T-cell lymphoma (EATL).
- •Hepatosplenic T-cell lymphoma (HSTCL).
- •Eastern Cooperative Oncology Group (ECOG) performance status of less than or equal to
- •Fluorodeoxyglucose (FDG)-avid disease by positron emission tomography (PET) imaging and measurable disease with at least 1 bidimensionally measurable lesion (>1.5 cm in its largest dimension) by computed tomography (CT).
- •Suitable venous access for the study-required blood sampling, including pharmacokinetic (PK) and immunogenicity sampling.
- •Clinical laboratory values as specified below at screening/baseline within 7 days before the first dose of study drug:
- •Total bilirubin must be ≤1.5 times the upper limit of normal (ULN) or ≤3 times the ULN for participants with Gilbert's disease or documented hepatic involvement with lymphoma.
- •Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) must be ≤3 times the ULN or ≤5 times the ULN for participants with an elevation that can be reasonably ascribed to the presence of metastatic disease in liver.
- •Serum creatinine must be <2.0 milligram per deciliter (mg/dL) and/or creatinine clearance or calculated creatinine clearance >40 milliliter (mL)/minute.
- •Hemoglobin must be ≥8 grams per deciliter (g/dL). (Red blood cell transfusion is allowed ≥14 days before assessment.)
- •Absolute neutrophil count >1.5×10^9/liter (L).
- •Platelet count ≥75×10^9/L (unless documented bone marrow involvement with lymphoma).
排除标准
- •Systemic anticancer therapy, including traditional Chinese medicine with antitumor indication for disease under study before the first dose of study drugs.
- •Major surgery within 28 days before the first dose of study drug.
- •Known human immunodeficiency virus (HIV)-positive status.
- •Known hepatitis B virus (HBV) surface antigen (HBsAg) seropositivity or active hepatitis C virus infection.
- •Note: Participants who have positive HBV core antibody and are HBsAg negative can be enrolled, but must have an undetectable HBV viral load.
- •Diagnosed or treated for another malignancy within 3 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease. Participants with nonmelanoma skin cancer or carcinoma in situ of any type are not excluded if they have undergone complete resection.
- •Any of the following cardiovascular conditions or values within 6 months before the first dose of study drug:
- •Left-ventricular ejection fraction <45%.
- •Myocardial infarction within 6 months of enrollment.
- •New York Heart Association Class III or IV heart failure.
- •Participants with current diagnosis of primary cutaneous CD30+ T-cell lymphoproliferative disorders and lymphomas. Participants with cutaneous anaplastic large cell lymphoma (ALCL) with extracutaneous tumor spread beyond locoregional lymph nodes are eligible (previous single-agent treatment to address cutaneous and locoregional disease is permissible).
- •Participants with mycosis fungoides (MF) [including transformed MF].
- •Uncontrolled diabetes mellitus.
- •Baseline peripheral neuropathy ≥Grade 2 (National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE], version 5.0).
- •History of progressive multifocal leukoencephalopathy (PML).
- •Previous treatment with brentuximab vedotin or CD30 monoclonal antibody.
研究组 & 干预措施
Brentuximab Vedotin + CHP
Brentuximab vedotin 1.8 mg/kg, intravenous (IV) infusion, within 1 hour of completing treatment with other IV agents, i.e., cyclophosphamide 750 mg/m^2 and doxorubicin 50 mg/m^2 IV, on Day 1 of each 21-day cycle, and prednisone 100 mg tablets, orally, on Days 1 through Day 5, for up to 8 cycles (6 months) or until progressive disease (PD), unacceptable toxicity, whichever occurs first.
干预措施: Brentuximab Vedotin (Drug)
Brentuximab Vedotin + CHP
Brentuximab vedotin 1.8 mg/kg, intravenous (IV) infusion, within 1 hour of completing treatment with other IV agents, i.e., cyclophosphamide 750 mg/m^2 and doxorubicin 50 mg/m^2 IV, on Day 1 of each 21-day cycle, and prednisone 100 mg tablets, orally, on Days 1 through Day 5, for up to 8 cycles (6 months) or until progressive disease (PD), unacceptable toxicity, whichever occurs first.
干预措施: Cyclophosphamide (Drug)
Brentuximab Vedotin + CHP
Brentuximab vedotin 1.8 mg/kg, intravenous (IV) infusion, within 1 hour of completing treatment with other IV agents, i.e., cyclophosphamide 750 mg/m^2 and doxorubicin 50 mg/m^2 IV, on Day 1 of each 21-day cycle, and prednisone 100 mg tablets, orally, on Days 1 through Day 5, for up to 8 cycles (6 months) or until progressive disease (PD), unacceptable toxicity, whichever occurs first.
干预措施: Doxorubicin (Drug)
Brentuximab Vedotin + CHP
Brentuximab vedotin 1.8 mg/kg, intravenous (IV) infusion, within 1 hour of completing treatment with other IV agents, i.e., cyclophosphamide 750 mg/m^2 and doxorubicin 50 mg/m^2 IV, on Day 1 of each 21-day cycle, and prednisone 100 mg tablets, orally, on Days 1 through Day 5, for up to 8 cycles (6 months) or until progressive disease (PD), unacceptable toxicity, whichever occurs first.
干预措施: Prednisone (Drug)
结局指标
主要结局
Percentage of Participants With Clinically Significant Vital Signs
时间窗: Up to approximately 7 months
Vital signs will include measurements of diastolic and systolic blood pressure, heart rate, and body temperature. Any value outside the normal range will be flagged for the attention of the investigator who will assess whether or not a flagged value is of clinical significance.
Overall Response Rate (ORR) by Independent Review Facility (IRF) Assessment per Revised Response Criteria for Malignant Lymphoma
时间窗: Up to approximately 7 months
ORR by IRF assessment following the completion of study treatment is defined as the percentage of participants who have achieved a complete response (CR) or partial response (PR) by IRF assessment using the International Working Group (IWG) Revised Response criteria following the completion of study treatment. CR is defined as disappearance of all evidence of disease. PR is defined as regression of measurable disease and no new sites.
Percentage of Participants who Experience at Least One Treatment Emergent Adverse Event (TEAE)
时间窗: Up to approximately 7 months
An adverse event (AE) is defined as any untoward medical occurrence in a participant administered a pharmaceutical product; it does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (e.g., 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 TEAE is defined as an adverse event that occurs after administration of the first dose of study treatment and up through 30 days after the last dose of study treatment.
Percentage of Participants With Clinically Significant Laboratory Test Values
时间窗: Up to approximately 7 months
Clinical laboratory tests will include hematocrit, hemoglobin, platelet (count), white blood cell (WBC) count, absolute neutrophil count (ANC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin (total), albumin, alkaline phosphatase, blood urea nitrogen, calcium, chloride, gamma glutamyl transferase, glucose, lactate dehydrogenase, phosphate, potassium, sodium, urate and creatinine evaluations. Any value outside the normal range will be flagged for the attention of the investigator who will assess whether or not a flagged value is of clinical significance.
次要结局
- CR Rate by IRF Assessment per Revised Response Criteria for Malignant Lymphoma(Up to approximately 7 months)
- 1-Year Progression Free Survival (PFS) Rate by IRF Assessment per Revised Response Criteria for Malignant Lymphoma(Up to approximately 12 months)
- 1-Year Overall Survival (OS) Rate(Up to approximately 12 months)
- ORR by IRF and Investigator Assessment per 2014 Lugano Classification(Up to approximately 7 months)
- CR Rate by IRF and Investigator Assessment per 2014 Lugano Classification(Up to approximately 7 months)
- Time to Response (TTR) by IRF and Investigator Assessment per 2014 Lugano Classification(Up to approximately 7 months)
- 1-Year PFS Rate by IRF and Investigator Assessment per 2014 Lugano Classification(Up to approximately 12 months)
- Duration of Response (DOR) by Investigator Assessment per 2014 Lugano Classification(Up to approximately 36 months)
- Serum Antibody-drug Conjugate (ADC) Concentration(Preinfusion and at multiple time points (Up to 96 hours [Cycle 1]/168 hours [Cycle 2]) postinfusion; Preinfusion up to Cycle 8, each cycle = 21 days)
- Plasma Monomethyl Auristatin E (MMAE) Concentration(Preinfusion and at multiple time points (Up to 96 hours [Cycle 1]/168 hours [Cycle 2]) postinfusion; Preinfusion up to Cycle 8, each cycle = 21 days)
- Percentage of Participants who are Antidrug Antibodies (ADA) Negative, ADA Transiently and Persistently Positive, ADA Titer, and Neutralizing Antidrug Antibody (Nab) Negative and Positive(Preinfusion on Day 1 of each cycle up to Cycle 8, each cycle = 21 days)