A Randomized, Controlled, Open-Label, Multicenter Phase 3 Study of the Bruton's Tyrosine Kinase (BTK) Inhibitor, Ibrutinib, Versus Temsirolimus in Subjects With Relapsed or Refractory Mantle Cell Lymphoma Who Have Received at Least One Prior Therapy
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 280
- 主要终点
- Progression Free Survival (PFS)
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of ibrutinib versus temsirolimus in patients with relapsed or refractory mantle cell lymphoma who received at least 1 prior chemotherapy regimen.
详细描述
This is a randomized (individuals assigned to study treatment by chance), open-label (identity of assigned study drug will be known), study to evaluate the efficacy and safety of ibrutinib when compared with temsirolimus in patients with relapsed or refractory mantle cell lymphoma (MCL) who have received at least 1 prior rituximab-containing chemotherapy regimen. Approximately 280 eligible patients will be randomly assigned in a 1:1 ratio and stratified (grouped) by the number of prior lines of therapy (1 or 2 versus >=3) and simplified MCL International Prognostic Index criteria to receive either ibrutinib by mouth (Treatment Arm A) or temsirolimus intravenous infusion (Treatment Arm B). The study will consist of screening, treatment, and posttreatment phases. Data will be collected on disease response to the treatment, progression-free survival, overall survival, subsequent anti-MCL therapies, patient reported outcomes, and medical resource utilization. Tumor samples, blood collected at multiple time points, and a bone marrow aspirate will be evaluated to identify markers predictive of response or resistance to ibrutinib. Serial pharmacokinetic (study of what the body does to a drug) samples will be collected as detailed in the protocol. Safety will be monitored throughout the study. Disease evaluations will be performed every 9 weeks for up to 15 months from the start of study drug, and every 24 weeks thereafter, until disease progression, death, or the clinical cutoff, whichever comes first. Patients who receive treatment with temsirolimus and have disease progression (confirmed by an Independent Review Committee) may be eligible to crossover and receive treatment with ibrutinib 560 mg orally, daily, on a 21-day cycle until disease progression, unacceptable toxicity, or study end. Data will be analyzed up to 3 years after the last patient is enrolled for the final follow-up.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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
- •Confirmed diagnosis of mantle cell lymphoma (MCL)
- •Received at least 1 prior rituximab-containing chemotherapy regimen (separate lines of therapy are defined as single or combination therapies that are either separated by disease progression or by a > 6 month treatment-free interval)
- •Documented relapse or disease progression following the last anti-MCL treatment
- •At least 1 measurable site of disease according to Revised Response Criteria for Malignant Lymphoma
- •Eastern Cooperative Oncology Group performance status grade 0 or 1
- •Protocol-defined hematology and biochemistry laboratory values
排除标准
- •Prior nitrosoureas within 6 weeks, chemotherapy within 3 weeks, therapeutic anticancer antibodies within 4 weeks, radio- or toxin-immunoconjugates within 10 weeks, radiation therapy or other investigational agents within 3 weeks, or major surgery within 4 weeks of randomization
- •Prior treatment with temsirolimus, other mTOR inhibitors, ibrutinib, or other Bruton's tyrosine kinase (BTK) inhibitors
- •Known central nervous system lymphoma
- •Received an allogeneic or autologous hematopoietic stem cell transplant <=6 months from the date of randomization and on immunosuppressive therapy or have evidence of active graft versus host disease
- •Diagnosed or treated for malignancy other than MCL, except: malignancy treated with curative intent and with no known active disease present for >=3 years before randomization, adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease, adequately treated cervical carcinoma in situ without evidence of disease
- •History of stroke or intracranial hemorrhage within 6 months prior to randomization
- •Requires anticoagulation with warfarin or equivalent vitamin K antagonist
- •Requires treatment with strong CYP3A inhibitor
- •Clinically significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease as defined by the New York Heart Association Functional Classification
- •Known history of human immunodeficiency virus (HIV) or active hepatitis C virus (HCV) or active hepatitis B virus (HBV) infection or any uncontrolled active systemic infection requiring intravenous antibiotics
- •Woman who is pregnant or breast-feeding
- •Any life-threatening illness, medical condition, or organ system dysfunction which, in the investigator's opinion, could compromise the patient's safety, interfere with the absorption or metabolism of ibrutinib capsules, or put the study outcomes at undue risk
研究组 & 干预措施
Ibrutinib
干预措施: Ibrutinib (Drug)
Temsirolimus
干预措施: Temsirolimus (Drug)
结局指标
主要结局
Progression Free Survival (PFS)
时间窗: Time from the date of randomization until the date of first documented evidence of progressive disease (or relapse for subjects who experience CR during the study) or death, whichever occurred first (approximately 48 months)
PFS is defined as the duration in months from the date of randomization to the date of progression disease (PD) or relapse from complete response (CR) or death whichever was reported first and was assessed based on the investigator assessment. Revised Response Criteria for Malignant Lymphoma categorizes the response of the treatment of a patient's tumour to CR (the disappearance of all evidence of disease), Relapsed Disease or PD (Any new lesion or increase by greater than or equal to \[\>=\] 50 percent \[%\] of previously involved sites from nadir).
次要结局
- Progression-Free Survival 2(Approximately up to 48 months)
- Time to Worsening in the Lymphoma Sub Scale of Functional Assessment of Cancer Therapy- Lymphoma (FACT-Lym)(Approximately up to 48 months)
- Overall Response Rate (ORR)(Approximately up to 48 months)
- Overall Survival (OS)(Approximately up to 48 months)
- Duration of Response(Approximately up to 48 months)
- Time-to-Next Treatment(Approximately up to 48 months)
- Number of Participants Affected With Treatment-emergent Adverse Events(Time from first dose of study drug until the last dose date + 30 days or the start of a subsequent anti-neoplastic therapy, whichever occur earlier (Approximately up to 4 years))