A Phase Ib Study of Ibrutinib in Combination With Obinutuzumab in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 54
- 试验地点
- 4
- 主要终点
- Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
研究概览
简要总结
This research study is evaluating a combination of two drugs, ibrutinib and obinutuzumab, as a possible treatment for Chronic Lymphocytic Leukemia (CLL).
详细描述
This research study is a Phase I clinical trial, which tests the safety of an investigational intervention and also tries to define the best order of administration of these two drugs. "Investigational" means that the intervention is being studied. The FDA (the U.S. Food and Drug Administration) has approved ibrutinib and obinutuzumab individually for the treatment of patients with Chronic Lymphocytic Leukemia, your type of cancer. However, the FDA has not approved the combination of these two drugs as a treatment for any disease.
Ibrutinib is a type of drug called a kinase inhibitor. It is believed to block a type of protein called a kinase that helps leukemia cells live and grow. By blocking this, it is possible that the study drug will kill cancer cells or stop them from growing.
Obinutuzumab is a type of drug called a monoclonal antibody. It is believed to attach to a protein called CD20 on the outside of a Chronic Lymphocytic Leukemia cell. By attaching to the cell, the antibody can cause the Chronic Lymphocytic Leukemia cell to die.
In this research study, the investigators are assessing the safety of various dosing regimens of ibrutinib and obinutuzumab. The investigators are trying to determine whether it is better to give one drug before the other or if they can be started at the same time.
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
- 未提供
排除标准
- •History of severe allergic or anaphylactic reactions to monoclonal antibody therapy
- •Prior treatment with either obinutuzumab or ibrutinib
- •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.
- •Low-risk prostate cancer on active surveillance
- •Concurrent systemic immunosuppressant therapy (eg, cyclosporine A, tacrolimus, etc., or chronic administration 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 ≤7 days before the first dose of study drug.
- •Known bleeding disorders or hemophilia.
- •History of stroke or intracranial hemorrhage within 6 months prior to enrollment.
- •Known history of HIV or active hepatitis C virus (HCV) or hepatitis B virus (HBV).
- •Any uncontrolled active systemic infection.
- •Major surgery within 4 weeks of first dose of study drug.
- •Currently active, clinically significant cardiovascular disease, such as uncontrolled arrhythmia or Class 3 or 4 CHF as defined by the NYHA Functional Classification; or a history of Myocardial Infarction, unstable angina, or acute coronary syndrome within 6 months prior to randomization.
- •Lactating or pregnant.
- •Patients receiving any other study agents
- •Patients with known Central Nervous System involvement
- •Baseline QT Interval Corrected by the Fridericia Correction Formula (QTcF) >480 ms unless Left Bundle Branch Block
- •Patients who require warfarin or other vitamin K antagonists for anticoagulation
- •Concurrent administration of strong inhibitors or inducers of CYP3A
研究组 & 干预措施
Arm A- obinutuzumab -> ibrutinib
Participants enrolled in Arm A will receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6. Participants will begin to take ibrutinib daily starting cycle 2 and will continue with daily ibrutinib until the end of treatment.
干预措施: Obinutuzumab (Drug)
Arm A- obinutuzumab -> ibrutinib
Participants enrolled in Arm A will receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6. Participants will begin to take ibrutinib daily starting cycle 2 and will continue with daily ibrutinib until the end of treatment.
干预措施: Ibrutinib (Drug)
Arm B- ibrutinib -> obinutuzumab
Participants enrolled in Arm B will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. Participants will begin to receive obinutuzumab weekly starting cycle 2, and will receive obinutuzumab monthly during cycles 3-7
干预措施: Obinutuzumab (Drug)
Arm B- ibrutinib -> obinutuzumab
Participants enrolled in Arm B will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. Participants will begin to receive obinutuzumab weekly starting cycle 2, and will receive obinutuzumab monthly during cycles 3-7
干预措施: Ibrutinib (Drug)
Arm C- obinutuzumab/ibrutinib
Participants enrolled in Arm C will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. At the same time, participants will begin to receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6.
干预措施: Obinutuzumab (Drug)
Arm C- obinutuzumab/ibrutinib
Participants enrolled in Arm C will begin to take ibrutinib daily starting cycle 1 and will continue with daily ibrutinib until the end of treatment. At the same time, participants will begin to receive obinutuzumab weekly starting cycle 1, and will receive obinutuzumab monthly during cycles 2-6.
干预措施: Ibrutinib (Drug)
结局指标
主要结局
Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v4.0
时间窗: Baseline to 6 Months
To assess the safety of 3 different dosing regimens of ibrutinib plus obinutuzumab in patients with relapsed/refractory CLL
次要结局
- Duration of Response(2 Years)
- Complete Response Rate(6 Months)
- Overall Response Rate(2 Years)
- Minimal residual disease (MRD) status in the bone marrow and blood(6 Months)
- Progression Free Survival(2 Years)
- Partial Response Rate(6 Months)
研究者
Matthew S. Davids, MD
Principal Investigator
Dana-Farber Cancer Institute