A Phase II Multicenter Single Arm Study to Evaluate the Efficacy and Safety of Single Agent Bruton's Tyrosine Kinase Inhibitor, Ibrutinib, in Patients With Relapsed Refractory Classical Hodgkin's Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 28
- 试验地点
- 4
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
This phase II trial evaluates how effective 560 mg of ibrutinib taken by mouth daily is in the treatment of classical Hodgkin lymphoma which recurs or does not respond to initial treatment. Ibrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth, by altering the environment around the tumor or by affecting the immune system.
详细描述
PRIMARY OBJECTIVES:
I. To determine the antitumor efficacy of single agent ibrutinib as measured by the overall response rate in patients with relapsed/refractory Hodgkin's lymphoma who have relapsed or not responded to chemotherapy, immunotherapy and/or radiation.
SECONDARY OBJECTIVES:
I. To assess duration of tumor control including duration of response (DOR) II. To assess progression free survival (PFS). III. To assess the safety and tolerability of 560mg of ibrutinib in Hodgkin lymphoma (HL) patients.
TERTIARY OBJECTIVES:
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
- 未提供
排除标准
- •Prior allogeneic Stem cell transplant within 6 months.
- •Active GVHD or concurrent treatment with immunosuppressive medications as prophylaxis for GVHD
- •Previous therapy with BTK inhibition
- •Known cerebral/meningeal disease
- •Nodular lymphocyte predominant Hodgkin's Lymphoma subtype
- •Concurrent therapy with other systemic anti-neoplastic or investigational agents
- •Patients with a known hypersensitivity to any excipient contained in the drug formulation
- •History of other malignancies, except:
- •Malignancy treated with curative intent and with no known active disease present for
- •≥3 years before the first dose of study drug and felt to be at low risk for recurrence by treating physician.
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
- •Adequately treated carcinoma in situ without evidence of disease.
- •Concurrent systemic immunosuppressant therapy (e.g., cyclosporine A, tacrolimus, etc., or chronic administration [>14 days] of >20 mg/day of prednisone) within 28 days of the first dose of study drug.
- •Vaccinated with live, attenuated vaccines within 4 weeks of first dose of study drug
- •Recent infection requiring systemic treatment that was completed ≤14 days before the first dose of study drug.
- •Unresolved toxicities from prior anti-cancer therapy, defined as having not resolved to Common Terminology Criteria for Adverse Event (CTCAE, version 4), grade ≤1, or to the levels dictated in the inclusion/exclusion criteria with the exception of alopecia.
- •Known bleeding disorders (e.g., von Willebrand's disease) or hemophilia.
- •History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- •Known history of human immunodeficiency virus (HIV) or active with hepatitis C virus (HCV) or hepatitis B virus (HBV). Subjects who are positive for hepatitis B core antibody or hepatitis B surface antigen must have a negative polymerase chain reaction (PCR) result before enrollment. Those who are PCR positive will be excluded.
- •Any uncontrolled active systemic infection
- •Major surgery within 4 weeks of first dose of study drug.
- •Any life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the subject's safety or put the study outcomes at undue risk.
- •Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 congestive heart failure as defined by the New York Heart Association Functional Classification; or a history of myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization
- •Unable to swallow capsules or malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease or ulcerative colitis, or partial or complete bowel obstruction.
- •Concomitant use of warfarin or other Vitamin K antagonists.
- •Requires treatment with a strong cytochrome P450 (CYP) 3A4/5 inhibitor
- •Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification
- •Lactating or pregnant
- •Unwilling or unable to participate in all required study evaluations and procedures.
- •Unable to understand the purpose and risks of the study and to provide a signed and dated informed consent form (ICF) and authorization to use protected health information (in accordance with national and local subject privacy regulations).
- •Potential subjects must be willing and able to adhere to the following prohibitions and restrictions during the course of the study to be eligible for participation. During the study, subjects should avoid consuming food and beverages containing grapefruit or Seville oranges as these contain certain ingredients that inhibit CYP3A4/5 enzymes.
研究组 & 干预措施
Treatment (ibrutinib)
Patients receive ibrutinib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (ibrutinib)
Patients receive ibrutinib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Pharmacological Study (Other)
Treatment (ibrutinib)
Patients receive ibrutinib PO QD. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: From date of study entry to date of progression or death up to 24 months
Overall response rate (ORR) defined as the proportion of participants having a complete (CR) and partial (PR) response. A one-sample binomial test will be used to assess ORR.
次要结局
- Duration of Response (DOR)(From date of documented tumor response, CR or PR, to date of disease progression or death, up to 24 months)
- Progression Free Survival (PFS)(From date of study entry to date of progression or death up to 24 months.)
研究者
Dipenkumar Modi
Principal Investigator
Barbara Ann Karmanos Cancer Institute