A Phase 2 Study of the Bruton's Tyrosine Kinase (Btk) Inhibitor, PCI-32765(Ibrutinib), in Relapsed and Refractory Patients With Chronic Lymphocytic Leukemia (CLL)/Small Lymphocytic Lymphoma (SLL) and B-cell Prolymphocytic Leukemia (B-PLL)
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 154
- 试验地点
- 1
- 主要终点
- Determine the 2 Year Progression-free Survival (PFS) of Single Agent PCI-32765 in Patients With Relapsed and Refractory CLL.
研究概览
简要总结
This is a Phase II, single institution open-label, non-randomized monotherapy study to evaluate the clinical efficacy and durable disease control of PCI-32765 administered to patients with relapsed/refractory CLL/SLL/PLL of all risk categories with patients having deletion 17p13 independently evaluated.
详细描述
This is a clinical trial, a type of research study, involving treatment with an investigational (experimental) drug called PCI-32765 (Ibrutinib), a "kinase inhibitor". "Kinases" are proteins that are inside of cells and help them to live and grow. The specific kinase inhibited or blocked by this study drug is believed to help blood cancer cells grow and live. By inhibiting or "blocking" the activity of this kinase, it is possible that the study drug may be able to kill the cancer cells or stop them from growing. This study will involve treating patients with chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or B-cell prolymphocytic leukemia (B-PLL) that has not responded to or has relapsed after standard treatment. This trial is studying how effective PCI-32765 is at treating CLL, SLL, or B-PLL and all the effects, good and/or bad, treatment with this drug has on patients and their cancers.
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
- •Confirmed diagnosis of relapsed/refractory CLL/SLL who require treatment and have failed at least one prior therapy.
- •Patients must have available results of interphase cytogenetics CLL fluorescent in situ hybridization (FISH) panel; the cytogenetic analysis must be done prior to starting therapy but after any recent therapy
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- •Life expectancy greater than 2 months
- •Bilirubin =< 1.5 X the institutional upper limit of normal unless due to Gilbert's disease or disease related to Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =< 2.5 X the institutional upper limit of normal unless disease related
- •Creatinine =< 1.5 X the institutional upper limit of normal unless disease related
- •Absolute neutrophil count (ANC) >= 0.75 X 10^9/L
- •Platelet count >= 30 X 10^9/L
- •Agree to use contraception during the study and for 30 days after the last dose of study drug if sexually active and able to bear children
- •Ability to understand and the willingness to sign a written informed consent document
- •Patients with uncontrolled or active infection requiring antibiotic therapy; patients with controlled infections who are receiving extended antibiotics or prophylactic therapy are not excluded
排除标准
- •Patients who have had chemotherapy, radiotherapy or immunotherapy within 4 weeks prior to the first dose of study drug (corticosteroids for disease-related symptoms allowed but doses equivalent to > 20 mg prednisone orally per day require 1 week washout before study drug administration or steroid dose must be equal to =< 20 mg prednisone orally daily)
- •Patients who have not recovered from adverse events of >= grade 3 toxicity due to agents administered more than 4 weeks ago
- •Receiving any other investigational agents
- •Previously randomized to any PCI-32765 clinical trial
- •Known secondary malignancy that limits survival to less than two years
- •Patients with malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction
- •Patients requiring anti-coagulation with warfarin or other Vitamin K antagonists or heparin products including low molecular weight heparin (LMWH)
- •Currently active, clinically significant hepatic impairment Child-Pugh class B or C according to the Child Pugh classification
- •Patients requiring treatment with a strong cytochrome P450 3A4/5 (CYP3A4/5) and/or cytochrome P450 2D6 (CYP2D6) inhibitor
- •Patients with a life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of PCI-32765 PO, or put the study outcomes at undue risk
- •Significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months of screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification
- •Active central nervous system (CNS) involvement by lymphoma
- •Pregnant or women who are breastfeeding
研究组 & 干预措施
Treatment (ibrutinib)
Patients will be treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) and not experiencing any unacceptable toxicity. Subjects with disease progression will be removed from the study. Correlative laboratory samples, quality of life assessment, and immunologic data would be collected over time of therapy.
干预措施: ibrutinib (Drug)
Treatment (ibrutinib)
Patients will be treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) and not experiencing any unacceptable toxicity. Subjects with disease progression will be removed from the study. Correlative laboratory samples, quality of life assessment, and immunologic data would be collected over time of therapy.
干预措施: Correlative laboratory samples (Other)
Treatment (ibrutinib)
Patients will be treated with PCI-32765 capsules administered orally once daily at a dose of 420 mg for 28 day cycles. Weekly monitoring during the first month will occur followed by monthly evaluations for 2 additional months. Monitoring for patients at this point would be every 3 months with monthly CBC(complete blood count)and phone follow-up with a co-investigator on the study. A standard questionnaire will be used in this monthly phone assessment. Patients will continue to receive the study drug indefinitely as long as they are deriving clinical benefit (Complete Response or Partial Response or Stable Disease) and not experiencing any unacceptable toxicity. Subjects with disease progression will be removed from the study. Correlative laboratory samples, quality of life assessment, and immunologic data would be collected over time of therapy.
干预措施: quality of life assessment (Other)
结局指标
主要结局
Determine the 2 Year Progression-free Survival (PFS) of Single Agent PCI-32765 in Patients With Relapsed and Refractory CLL.
时间窗: up to 2 years
We will summarize our findings for this endpoint independently as well within each cohort (del17p vs other cytogenetic groups). We will evaluate the proportion of patients who are progression-free and alive at two years or have gone on to transplant (treatment successes) over the total number of evaluable patients; eligible patients who received at least one dose of therapy are considered evaluable. Assuming that the number of treatment successes as defined above is binomially distributed, we will also include 95% binomial confidence intervals for the estimates corresponding to each cohort.
次要结局
- Resistance Studies of Ibrutinib(Up to 4 years)
- Cancer-Specific Stress as Measured by the Impact of Event Scale-Revised (IES-R)(Up to 2 years)
- Cognitive-Affective Depressive Symptoms as Measured by the Beck Depression Inventory-2nd Edition (BDI-II)(at 5 months)
- Decrease in Immune Suppression of CLL Cells(up to 3 months)
- Mental Health Quality of Life Was Measured by the Mental Component Summary Score of the Medical Outcomes Study(at 5 months)
- Percentage of Patients With Overall Survival (OS)(2 years)
- Effectiveness of Ibrutinib Bridging Patients to Allogeneic Stem Cell Transplant and Outcome of Patients Following This Intervention(Up to 2 years)
- Best Overall Response Rate Using the Revised International Workshop on Chronic Lymphocytic Leukemia (IWCLL) Working Group Guidelines(up to 2 years)
- 2-year Kaplan-Meier Estimate of OS for Relapsed and Refractory CLL Patients Treated With Single Agent PCI-32765(2 years)
- Number of Patients With Adverse Events, Graded According to the NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0(Up to 2 years post treatment)
- Number of Patients With 6 Month ORR of Single Agent Ibrutinib in Relapsed and Refractory CLL Patients(Up to 6 months)
- Negative Mood Quality of Life Measured by a 37-item Questionnaire(at 5 months)
- Fatigue Symptom Inventory (FSI) Interference Quality of Life as Measured by a 11-item Total Disruption Index Sub Scale of Fatigue Symptoms Inventory(at 5 months)
- Physical Health Quality of Life as Measured by a 12 Item Short-Form Health Survey(up to 5 months)
- Sleep Through Quality of Life as Measured by a Medical Outcomes Study-Sleep Scale(at 5 months)
研究者
Kami Maddocks, MD
Principal Investigator
Ohio State University Comprehensive Cancer Center