A Multicenter, Single-arm, Open-label, Phase 4 Study to Evaluate the Safety and Efficacy of Brentuximab Vedotin Plus Doxorubicin, Vinblastine and Dacarbazine in Indian Patients With Untreated Stage 3/4 Classical Hodgkin Lymphoma
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 124
- 试验地点
- 11
- 主要终点
- Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Drug Reactions (ADRs), and Unexpected ADRs
研究概览
简要总结
The main aim of this study is to check how safe brentuximab vedotin is in adults with untreated Hodgkin Lymphoma (HL) when given together with doxorubicin (Adriamycin), vinblastine and dacarbazine therapy ('AVD'). Another aim is to learn how well treatment of brentuximab vedotin plus AVD works.
All participants will receive brentuximab vedotin plus AVD for approximately 6 months. Participants will undergo tests like Echocardiography (ECHO) and pulmonary function testing (PFT) during the study. ECHO is a test that uses ultrasound to show how the heart muscle and valves are working; PFT is a test to check how well a participant's lungs work.
Each participant will undergo a final health status check 2 months after the last treatment with brentuximab vedotin plus AVD.
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
- •Treatment-naïve, Hodgkin lymphoma (HL) participants with Ann Arbor Stage 3 or 4 disease.
- •Note: Participants must have histologically confirmed classical HL according to the current world health organization classification.
- •Participants must have bidimensional measurable disease as documented by radiographic technique (spiral computed tomography [CT] preferred) per the international working group revised criteria for response assessment for malignant lymphoma.
- •Male or female participants 18 years or older.
- •Eastern cooperative oncology group (ECOG) performance status less than or equal to (≤)
- •Female participants who:
- •Are postmenopausal for at least 1 year before the screening visit, OR
- •Are surgically sterile, OR
- •If they are of childbearing potential, agree to practice 1 highly effective method and 1 additional effective (barrier) method of contraception at the same time, from the time of signing of the informed consent form (ICF) through 6 months after the last dose of study drug, OR
- •Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together).
- •Male participants, even if surgically sterilized (i.e., status post-vasectomy), who:
- •Agree to practice effective barrier contraception during the entire study treatment period and through 6 months after the last dose of study drug, OR
- •Agree to practice true abstinence when this is in line with the preferred and usual lifestyle of the participant. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods for the female partner], withdrawal, spermicides only, and lactational amenorrhea are not acceptable methods of contraception. Female and male condoms should not be used together).
- •Voluntary written 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 participant at any time without prejudice to future medical care.
- •Clinical laboratory values as specified below within 7 days before the first dose of study drug:
- •Absolute neutrophil count greater than or equal to (≥)1,000 per microliter (1,000/μL) unless there is known HL marrow involvement
- •Platelet count ≥75,000/μL unless there is known HL marrow involvement
- •Total bilirubin must be lesser than (<)1.5 x upper limit of the normal range (ULN) unless the elevation is known to be due to Gilbert syndrome.
- •Alanine Aminotransferase (ALT) or aspartate aminotransferase (AST) must be <3.0 x ULN. An AST and ALT may be elevated up to 5 times the ULN if their elevation can be reasonably ascribed to the presence of HL in liver.
- •Note: Moderate or severe hepatic disease patients will be excluded based upon Child-Pugh criteria.
- •Serum creatinine must be <2.0 milligrams per deciliter (mg/dL) and/or creatinine clearance or calculated creatinine clearance >30 mL/minute (Cockcroft-Gault Equation).
- •Hemoglobin must be ≥8 grams per deciliter (g/dL).
排除标准
- •Female participants who are both lactating and breastfeeding or who 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 this 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 medications.
- •Any sensory or motor peripheral neuropathy.
- •Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within 2 weeks prior to first study drug dose.
- •Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy (e.g., immunoglobulin replacement, other monoclonal antibody therapies) within 12 weeks of first study drug dose.
- •Previously treated with brentuximab vedotin.
- •Any contraindications to the concomitant chemotherapy regimens (doxorubicin, vinblastine, and dacarbazine).
- •Known hypersensitivity to recombinant proteins, murine proteins, or to any excipient contained in the drug formulation of brentuximab vedotin or any component of doxorubicin, vinblastine, and dacarbazine (AVD).
- •Known human immunodeficiency virus (HIV) positive.
- •Known hepatitis B surface antigen-positive, or known or suspected active hepatitis C infection.
- •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:
- •A left-ventricular ejection fraction <50%
- •Myocardial infarction within 2 years of enrollment
- •New York Heart Association (NYHA) Class 3 or 4 heart failure. Evidence of current uncontrolled cardiovascular conditions, including cardiac arrhythmias, congestive heart failure (CHF), angina, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
研究组 & 干预措施
Brentuximab Vedotin 1.2 mg/kg
Participants will receive 1.2 milligrams per kilogram (mg/kg) brentuximab vedotin intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle, within 1 hour after completion of treatment with other agents [25 milligrams per meter square (mg/m^2) doxorubicin, 6 mg/m^2 vinblastine and 375 mg/m^2 dacarbazine IV infusions] for a maximum of 6 cycles.
干预措施: Doxorubicin (Drug)
Brentuximab Vedotin 1.2 mg/kg
Participants will receive 1.2 milligrams per kilogram (mg/kg) brentuximab vedotin intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle, within 1 hour after completion of treatment with other agents [25 milligrams per meter square (mg/m^2) doxorubicin, 6 mg/m^2 vinblastine and 375 mg/m^2 dacarbazine IV infusions] for a maximum of 6 cycles.
干预措施: Dacarbazine (Drug)
Brentuximab Vedotin 1.2 mg/kg
Participants will receive 1.2 milligrams per kilogram (mg/kg) brentuximab vedotin intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle, within 1 hour after completion of treatment with other agents [25 milligrams per meter square (mg/m^2) doxorubicin, 6 mg/m^2 vinblastine and 375 mg/m^2 dacarbazine IV infusions] for a maximum of 6 cycles.
干预措施: Vinblastine (Drug)
Brentuximab Vedotin 1.2 mg/kg
Participants will receive 1.2 milligrams per kilogram (mg/kg) brentuximab vedotin intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle, within 1 hour after completion of treatment with other agents [25 milligrams per meter square (mg/m^2) doxorubicin, 6 mg/m^2 vinblastine and 375 mg/m^2 dacarbazine IV infusions] for a maximum of 6 cycles.
干预措施: Brentuximab Vedotin (Drug)
结局指标
主要结局
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), Adverse Drug Reactions (ADRs), and Unexpected ADRs
时间窗: Up to 40 weeks
An AE is defined as any untoward medical occurrence in a clinical investigation patient administered a drug; it does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product whether or not it is related to the medicinal product. An SAE is any AE that results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in significant disability or incapacity, is a congenital anomaly/birth defect or is a medically important event. ADRs are defined as AEs which are in the investigator's opinion of causal relationship to the study treatment. An unexpected ADR is an ADR with the nature, severity, or outcome which is not consistent with summary of product characteristics.
次要结局
- Percentage of Participants Achieving Complete Remission (CR)(Up to 35 weeks)
- Objective Response Rate (ORR)(Up to 35 weeks)
- Positron Emission Tomography (PET) Negativity Rate at Cycle 2(Days 20 to 28 of Cycle 2 (cycle length=28 days))
- Progression Free Survival (PFS)(Up to 40 weeks)
- Overall Survival (OS)(Up to 40 weeks)
- Disease Free Survival(Up to 40 weeks)
- Event Free Survival(Up to 40 weeks)
- Duration of Response (DOR)(Up to 40 weeks)
- Duration of Complete Remission (DOCR)(Up to 40 weeks)