A prospective, randomized, multicenter, comparative, double-blind, parallel group study to evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of test brentuximab vedotin (ZRC-3318) with reference brentuximab vedotin (Adcetris®), in combination with chemotherapy, in patients with previously untreated stage III or IV classical Hodgkin lymphoma
试验速览
- 阶段
- 3 期
- 状态
- 尚未招募
- 入组人数
- 201
- 试验地点
- 39
- 主要终点
- Independently assessed objective response rate (i.e., complete response [CR] + partial response [PR]) using the Lugano classification
研究概览
简要总结
This is a phase III, multicenter, randomized, double-blind, parallel comparator study to determine the efficacy, safety, pharmacokinetics, and immunogenicity of a biosimilar of brentuximab vedotin (ZRC-3318), developed by Zydus Lifesciences Limited – India, in comparison with reference brentuximab vedotin (Adcetris®), when administered in combination with chemotherapy, in patients with previously untreated stage III or IV classical Hodgkin lymphoma.
In this study, eligible participants will be enrolled in either of the following two arms:
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Arm 1, in this arm, participants will receive test brentuximab vedotin + chemotherapy
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Arm 2, in this arm, participants will receive reference brentuximab vedotin + chemotherapy
Test or reference brentuximab vedotin will be administered at a dose of 1.2 mg/kg (up to a maximum of 120 mg) as an intravenous infusion (over 30 minutes) every 2 weeks (Day 1 & Day 15 of each 28-day cycle with defined window period) until a maximum of 12 doses (six cycles).
Other than the difference in investigational drug molecule (test versus reference brentuximab vedotin), all other study schedules and procedures will be identical between arm 1 and arm 2.
AVD is to be administered first, in the stated order, per institutional guidelines, followed by administration of brentuximab vedotin. If an investigator needs to choose a different order of administration of study drugs, this must first be discussed with Sponsor’s medical expert. The order of administration must not change for patients of the PK evaluation arm.
Granulocyte-colony stimulating factor (G-CSF) will also be administered prophylactically during each chemotherapy cycle as per the investigator’s discretion.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant, Investigator and Outcome Assessor Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Men or women aged greater than equal to 18 years.
- •Those who voluntarily provide written informed consent (approved by an Institutional Review Board or Institutional Ethics Committee) before any study specific procedures; this demonstrates that he or she understands the purpose and procedures of the study and is willing to participate in the study.
- •Individuals with histologically confirmed classical HL (cHL) according to the current World Health Organization Classification (nodular sclerosis, mixed cellularity, lymphocyte rich, lymphocyte depleted, or cHL, not otherwise specified [NOS]).
- •Treatment naïve patients with HL with modified Ann Arbor Stage III or IV disease (refer appendix I).
- •Those with Eastern Cooperative Oncology Group (ECOG) performance status 0 or
- •Those who have clinically palpable lymph node or spleen or liver or other extra nodal sites with increased FDG uptake on PET-CT as per the Lugano classification.
- •Individuals with the following laboratory results: a.
- •Absolute neutrophil count greater than equal to 1500 cells per mm3, unless there is documented involvement of Hodgkin’s lymphoma in the bone marrow b.
- •Platelet count greater than equal to 75000 cells per mm3, unless there is documented involvement of Hodgkin’s lymphoma in the bone marrow c.
- •Hemoglobin greater than equal to 8.0 g per dL d.
- •Total bilirubin less than2X upper limit of normal (ULN) e.
- •Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) less than equal to 5X ULN f.
- •Serum creatinine less than 2.0 mg per dL and/or creatinine clearance greater than 40 mL per min based on Cock croft Gault glomerular filtration rate estimation (140 age) × (weight in kg) × (0.85 if female) per (72 × serum creatinine).
排除标准
- •Participants with nodular lymphocyte predominant Hodgkin lymphoma.
- •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 motor or sensory peripheral neuropathy.
- •Any active systemic viral, bacterial, or fungal infection requiring systemic antibiotics within two weeks prior to the first dose of study drugs.
- •Prior immunosuppressive chemotherapy, therapeutic radiation, or any immunotherapy (e.g., immunoglobulin replacement, other monoclonal antibody therapies) within 12 weeks of the first dose of study drugs.
- •History of other malignancy within previous 3 years before the first dose or previously diagnosed with another malignancy and have any evidence of residual disease, except for appropriately treated carcinoma in situ of any type and non-melanoma skin carcinoma.
- •Positive Hepatitis B serology (either HBsAg or anti-HBc) or Hepatitis C serology (positive HCVAb or HCV RNA) indicative of previous or current infections.
- •History of 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).
- •Any of the following cardiovascular conditions or values within 6 months before the first dose of study drugs: a.
- •Left ventricular ejection fraction less than equal to 50 percentage by 2D echocardiography (2D ECHO) b.
- •Myocardial infarction within 2 years of randomization c.
- •New York Heart Association (NYHA) class III or IV heart failure d.
- •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
- •Receipt of any investigational drug within 30 days or five half lives (whichever is longer) prior to the first dose of study drugs or enrolment in another interventional clinical study.
- •Documented medical history of a poorly controlled/clinically significant medical condition or laboratory parameters, such as but not limited to, poorly controlled diabetes (HbA1c greater than 8 percentage despite medical treatment), active peptic ulcer disease, interstitial lung disease, blood coagulation disorders, or other relevant medical disease, such as a neurological, psychiatric, pulmonary, gastrointestinal, or endocrine disease or a history of clinically significant hematological, renal, or liver disease or any other condition that, in the opinion of the investigator, would put the patient at risk by participation in the trial or deemed by the clinician to be likely to interfere with a participant’s compliance and ability to provide informed consent, cooperate, or participate in the study, or to interfere with the interpretation of the results.
结局指标
主要结局
Independently assessed objective response rate (i.e., complete response [CR] + partial response [PR]) using the Lugano classification
时间窗: Day 1 to Day 155
次要结局
- Comparative clinical activity at week 24 between the two treatment arms by measuring progression free survival (PFS), overall survival (OS), and duration of response (DOR)(Day 1 to Day 169)
- Pharmacokinetic parameters of brentuximab vedotin, MMAE, and Tab in blood/plasma(Day 1 to Day 155)
- Immunogenicity(Day 1, Day 85 and Day 169)
- Treatment emergent adverse events(Day 1 to Day 169)
研究者
Dr Deven V Parmar
Zydus Lifesciences Ltd