A Phase II Study of Ibrutinib, Nivolumab and Blinatumomab in Richter Transformation
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Number of Participants With a Response
研究概览
简要总结
The goal of this clinical research study is to learn if blinatumomab can help to control Richter Transformation (RT, a type of blood cancer). The safety of this drug will also be studied.
This is an investigational study. Blinatumomab is FDA approved and commercially available for the treatment of acute lymphoblastic leukemia (ALL). It is investigational to use blinatumomab to treat patients with RT. The study doctor can explain how the study drug is designed to work.
Up to 21 participants will be enrolled in this study. All will take part at MD Anderson.
详细描述
Study Drug Administration:
The study has 2 study cycles. Cycle 1 is 8 weeks, followed by a 4-8 week break, and then Cycle 2 is 4 weeks.
If you are found to be eligible to take part in this study, you will receive blinatumomab by a central venous catheter (CVC) continuously (non-stop) for 1-2 cycles, depending on how you are responding to the study drug. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. Your doctor will explain this to you in more detail, and you will be required to sign a separate consent form for this procedure.
During Cycle 1, the blinatumomab infusion will be started in the hospital. You will be in the hospital for up to at least 16 nights/17 days so that you can be checked for side effects. During Cycle 2, the blinatumomab infusion will also be started in the hospital. You will be in the hospital for at least 2 nights/3 days. Your doctor will decide when you can leave the hospital. Also, if treatment is interrupted for more than 4 hours, for any reason, you will need to be admitted to the hospital to restart the treatment.
Blinatumomab will be delivered by a small pump, which you will carry with you for the whole time you receive the drug. You will be given a shoulder or belt bag to hold the pump and infusion bag. You will be able to wear regular clothes, walk around, and perform daily living activities. You will be given instructions for taking a shower and other activities. There will be some things that you should not do, such as go swimming. The study staff will give you more information on activities you should not do while receiving the drug.
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
- •Patients with previously treated CLL and biopsy-proven Richter's transformation with DLBCL histology according to IWCLL criteria (Richter Transformation - RT) and CD19 positive by flow cytometry OR immunohistochemistry.
- •Eastern Co-operative Oncology Group (ECOG) performance status < or =
- •Age > or =18 years at the time of informed consent.
- •Able to provide informed consent and be willing to participate in study schedule and events.
排除标准
- •Other active malignancy receiving systemic therapy.
- •History or presence of clinically relevant disorder affecting the CNS such as epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome, or psychosis, with the exception of a history of CNS lymphoma that is controlled with intrathecal therapy.
- •Known active DLBCL in the CNS (confirmed by CSF analysis).
- •Current autoimmune disease requiring >/= 20mg/day of prednisone or systemic immunosuppressive therapy (eg. with cyclosporine or azathioprine).
- •Allogeneic HSCT within 24 weeks before the start of protocol-specified therapy.
- •Active Graft-versus-Host Disease (GvHD), grade 2-4 according to the Glucksberg criteria, active chronic GvHD requiring systemic treatment or requirement for GvHD prophylaxis with cyclosporine or tacrolimus.
- •Cancer chemotherapy within 2 weeks before start of protocol-specified therapy, with the exception of intrathecal chemotherapy, dexamethasone, and oral small molecule inhibitors such as BTK-inhibitor, PI3K-inhibitor, or Bcl-2-inhibitor, which are allowed until the start of protocol-specified therapy). In addition, any subject whose organ toxicity (excluding hematologic) from prior treatment has not resolved to no more than CTCAE grade
- •Radiotherapy within 2 weeks before the start of protocol-specified therapy.
- •Abnormal screening laboratory values as defined as following: a) ALT (SGOT) and/or ALT (SGPT) and/or ALP > or =5 x upper limit of normal (ULN); b) Total bilirubin > or = 1.5 x ULN, unless due to Gilbert's disease; c) Creatinine > or = 2.0 x ULN or creatinine clearance <50 mL/min (calculated).
- •Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus (HBsAg positive) or hepatitis C virus (anti-HCV positive).
- •Patient is pregnant or breast feeding.
- •Woman of childbearing potential and is not willing to use 2 highly effective methods of contraception while receiving protocol-specified therapy and for an additional 24 hours after the last dose of protocol-specified therapy.
- •Male who has a female partner of childbearing potential, and is not willing to use 2 highly effective forms of contraception while receiving protocol-specified therapy and for at least an additional 24 hours after the last dose of protocol-specified therapy.
- •Male who has a pregnant partner, and is not willing to use a condom during sexual activity while receiving protocol-specified therapy and for 3 months after the last dose of protocol-specified therapy.
- •Currently receiving treatment in another investigational device or drug study.
- •Subject previously treated with blinatumomab.
- •History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the Principal Investigator would pose a risk to subject safety or interfere with the study evaluation, procedures or completion.
研究组 & 干预措施
Ibrutinib, Nivolumab and Blinatumomab
2 (8week) cycles of ibrutinib, nivolumab and blinatumomab. 9 (4week) cycles ibrutinib and nivolumab. Maintenance with ibrutinib monotherapy until disease progression following completion of nivolumab.
Ibrutinib treatment will begin cycle 1, day 1 at 420mg/d. Nivolumab for up to a total of 52 weeks. Dosing will be 240mg IV every 2 weeks, commencing on day 1 until 2nd response assessment, then 480mg IV every 4 weeks.
blinatumomab continuous IV infusion, starting day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week blinatumomab treatment-free interval. Hospitalization in cycle 1 on day 15-31 (first 17 days of blinatumomab therapy). Blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28, followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days. Blinatumomab in cycle 2 will be administered at a dose of 112 mcg/day from day 1-28.
干预措施: Blinatumomab (Drug)
Ibrutinib, Nivolumab and Blinatumomab
2 (8week) cycles of ibrutinib, nivolumab and blinatumomab. 9 (4week) cycles ibrutinib and nivolumab. Maintenance with ibrutinib monotherapy until disease progression following completion of nivolumab.
Ibrutinib treatment will begin cycle 1, day 1 at 420mg/d. Nivolumab for up to a total of 52 weeks. Dosing will be 240mg IV every 2 weeks, commencing on day 1 until 2nd response assessment, then 480mg IV every 4 weeks.
blinatumomab continuous IV infusion, starting day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week blinatumomab treatment-free interval. Hospitalization in cycle 1 on day 15-31 (first 17 days of blinatumomab therapy). Blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28, followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days. Blinatumomab in cycle 2 will be administered at a dose of 112 mcg/day from day 1-28.
干预措施: Dexamethasone (Drug)
Ibrutinib, Nivolumab and Blinatumomab
2 (8week) cycles of ibrutinib, nivolumab and blinatumomab. 9 (4week) cycles ibrutinib and nivolumab. Maintenance with ibrutinib monotherapy until disease progression following completion of nivolumab.
Ibrutinib treatment will begin cycle 1, day 1 at 420mg/d. Nivolumab for up to a total of 52 weeks. Dosing will be 240mg IV every 2 weeks, commencing on day 1 until 2nd response assessment, then 480mg IV every 4 weeks.
blinatumomab continuous IV infusion, starting day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week blinatumomab treatment-free interval. Hospitalization in cycle 1 on day 15-31 (first 17 days of blinatumomab therapy). Blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28, followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days. Blinatumomab in cycle 2 will be administered at a dose of 112 mcg/day from day 1-28.
干预措施: Ibrutinib (Drug)
Ibrutinib, Nivolumab and Blinatumomab
2 (8week) cycles of ibrutinib, nivolumab and blinatumomab. 9 (4week) cycles ibrutinib and nivolumab. Maintenance with ibrutinib monotherapy until disease progression following completion of nivolumab.
Ibrutinib treatment will begin cycle 1, day 1 at 420mg/d. Nivolumab for up to a total of 52 weeks. Dosing will be 240mg IV every 2 weeks, commencing on day 1 until 2nd response assessment, then 480mg IV every 4 weeks.
blinatumomab continuous IV infusion, starting day 15 of cycle 1 and day 1 of cycle 2, for 2 courses of 4 weeks each separated by a 2 week blinatumomab treatment-free interval. Hospitalization in cycle 1 on day 15-31 (first 17 days of blinatumomab therapy). Blinatumomab will be initiated at 9mcg/day from day 15-21, followed by 28 mcg/day from day 22-28, followed by 112 mcg/day from day 29-42. In cycle 2, patients will be admitted for the first 3 days. Blinatumomab in cycle 2 will be administered at a dose of 112 mcg/day from day 1-28.
干预措施: Nivolumab (Drug)
结局指标
主要结局
Number of Participants With a Response
时间窗: 2 months
Response is defined as complete remission (CR) plus partial remission (PR). Complete Remission (CR) is Lymph nodes None \>/= 1.5 cm, Spleen size \< 13 cm; normal liver size, the absence of constitutional symptoms, normal circulating lymphocyte count, platelets \>/= 100 x 10\^9/L, Hemoglobin \>/= 11.0 g/dL (absence of transfusion and without erythropoietin) and marrow normocellular, no CLL cells and no B-lymphoid nodules. Partial Remission (PR) is any two of the following must decrease \>/= 50% from baseline: lymph nodes, Liver and/or spleen size, circulating lymphocyte count in addition to one of the following: platelets \>/= 100 x 10\^9/L or \>/= 50% increase from baseline, Hemoglobin \>/= 11.0 g/dL or \>/= 50% increase from baseline or marrow presence of CLL cells, or of B-lymphoid nodules, or not done.
次要结局
- Overall Survival(Up to 4 years, 8 Months)
- Number of Participants to Achieve Complete Remission(Up to 4 years, 8 months)
- Progression Free Survival(Up to 4 years, 8 months)