A Phase II Study of Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) in Previously Treated Patients With Chronic Lymphocytic Leukemia (CLL)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Number of Participants With an Overall Response
研究概览
简要总结
The goal of this clinical research study is to learn if the combination of fludarabine, cyclophosphamide, alemtuzumab, and rituximab is effective in treating chronic lymphocytic leukemia in patients who have already been treated with chemotherapy.
Primary Objectives:
Evaluate the therapeutic efficacy, including the complete remission (CR), nodular partial remission (NPR), and partial remission (PR) rates (overall response) of combined cyclophosphamide, fludarabine, alemtuzumab, and rituximab (CFAR) in previously treated patients with Chronic Lymphocytic Leukemia (CLL).
Second Objectives:
- Assess the toxicity profile of CFAR in previously treated patients with CLL.
- Monitor for infection and determine incidence and etiology of infection including cytomegalovirus in patients treated with CFAR.
- Evaluate molecular remission by polymerase chain reaction (PCR) for the clonal immunoglobulin heavy chain variable gene in responding patients treated with CFAR.
- Assess immune parameters, including pretreatment, during treatment, and post-treatment blood T-cell counts and subset distribution and serum immunoglobulin levels in patients treated with CFAR.
详细描述
Fludarabine is a chemotherapy drug that is approved for the treatment of CLL. Cyclophosphamide is also a chemotherapy drug that is commonly used in the treatment of CLL. Rituximab and alemtuzumab are special proteins that specifically target and attach to proteins on leukemia cells. These targeted proteins may also be present on normal blood cells. When these drugs bind to the proteins on leukemia cells, they may help to stop or slow the growth of the disease. The combination of fludarabine, cyclophosphamide and rituximab has been used in the treatment of CLL. The purpose of this study is to determine if there is added benefit with the addition of alemtuzumab to this combination.
Before treatment starts, you will have a complete physical exam, including blood tests (about 3 tablespoons). You may have either a chest x-ray or a computed tomography (CT) scan if your doctor feel this is necessary. If you have not had a bone marrow sample collected in the past 4 months, you will have a bone marrow sample collected at this time. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anaesthetic and a small amount of bone marrow is withdrawn through a large needle. Women who are able to have children must have a negative blood pregnancy test.
During the study, you will have up to 6 "cycles" of treatment. A cycle is made up of treatment with the study drugs for 5 days in a row, then around 31/2 weeks (23 days) of no treatment with the study drugs. On Days 1, 3, and 5 of each cycle you will receive alemtuzumab through a needle in a vein. On Day 2 of each cycle you will receive rituximab through a needle in a vein. Cyclophosphamide and fludarabine will be given separately on Days 3, 4, and 5 of each cycle through a needle in a vein. In addition to the study drugs, you may also be given fluids by vein. The combination treatment will be repeated every 4 weeks (one cycle) for a total of up to 6 cycles. This treatment will be given on an outpatient basis. The injections for each daily treatment visit should take less than 6 hours.
You will receive acetaminophen (Tylenol) by mouth and diphenhydramine hydrochloride (Benadryl) by mouth or vein 30 - 60 minutes before each dose of rituximab and alemtuzumab. You will also receive hydrocortisone (a steroid) by vein before each dose of alemtuzumab. These drugs will be used to help decrease side effects. If side effects occur during a treatment, the doses of the drugs may be adjusted (up or down) until the symptoms are gone. Also, if you experience side effects during treatment, you must stay in the clinic for 2 hours after the drug is given to be observed.
If you begin to experience side effects due to treatment, the dose(s) of the drug(s) may be lowered or the treatment may be temporarily stopped until the symptoms are gone.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients must have been diagnosed with CLL by immunophenotyping and flow cytometry analysis of blood or bone marrow demonstrating a monoclonal population of CD5 and CD19 positive cells.
- •All patient must have been previously treated with chemotherapy.
- •All patients with Rai stage III-IV are eligible for treatment with this protocol. - OR - All patients with Rai stage 0-II who meet one or more indication for treatment as defined by the NCI-sponsored Working Group are eligible for treatment with this protocol.
- •All patients must have a Zubrod performance status of 0-
- •All patients must have adequate renal and hepatic function (serum creatinine <2mg/dL; total bilirubin <2.5mg/dL). Patients with renal or liver dysfunction due to organ infiltration by lymphocytes may be eligible after discussion with the Principle Investigator and appropriate dose adjustment considered.
- •Patients may not receive concurrent chemotherapy, radiotherapy, or immunotherapy. Localized radiotherapy to an area not compromising bone marrow function does not apply, nor do hematopoietic growth factors such as erythropoietin, Granulocyte colony-stimulating factor (G-CSF or GCSF, GM-CSF etc).
- •Patients must not have untreated or uncontrolled life-threatening infection.
- •Patients must sign informed consent.
排除标准
- 未提供
研究组 & 干预措施
CFAR
CFAR: Cyclophosphamide 250 mg/m^2/day intravenous (IV) Days 3-5, Fludarabine 25 mg/m^2/day IV Days 3-5, Alemtuzumab 30 mg IV Days 1, 3 and 5 over 2-4 hours, repeated every four weeks for a total of 6 planned cycles, and Rituximab Cycle 1 (Week 1): 375 mg/m^2/day IV Day 2 over 4- 6 hours, Cycle 2 - 6 (Week 1): 500 mg/m^2/day IV Day 2 over 4- 6 hours.
干预措施: Fludarabine (Drug)
CFAR
CFAR: Cyclophosphamide 250 mg/m^2/day intravenous (IV) Days 3-5, Fludarabine 25 mg/m^2/day IV Days 3-5, Alemtuzumab 30 mg IV Days 1, 3 and 5 over 2-4 hours, repeated every four weeks for a total of 6 planned cycles, and Rituximab Cycle 1 (Week 1): 375 mg/m^2/day IV Day 2 over 4- 6 hours, Cycle 2 - 6 (Week 1): 500 mg/m^2/day IV Day 2 over 4- 6 hours.
干预措施: Cyclophosphamide (Drug)
CFAR
CFAR: Cyclophosphamide 250 mg/m^2/day intravenous (IV) Days 3-5, Fludarabine 25 mg/m^2/day IV Days 3-5, Alemtuzumab 30 mg IV Days 1, 3 and 5 over 2-4 hours, repeated every four weeks for a total of 6 planned cycles, and Rituximab Cycle 1 (Week 1): 375 mg/m^2/day IV Day 2 over 4- 6 hours, Cycle 2 - 6 (Week 1): 500 mg/m^2/day IV Day 2 over 4- 6 hours.
干预措施: Alemtuzumab (Drug)
CFAR
CFAR: Cyclophosphamide 250 mg/m^2/day intravenous (IV) Days 3-5, Fludarabine 25 mg/m^2/day IV Days 3-5, Alemtuzumab 30 mg IV Days 1, 3 and 5 over 2-4 hours, repeated every four weeks for a total of 6 planned cycles, and Rituximab Cycle 1 (Week 1): 375 mg/m^2/day IV Day 2 over 4- 6 hours, Cycle 2 - 6 (Week 1): 500 mg/m^2/day IV Day 2 over 4- 6 hours.
干预措施: Rituximab (Drug)
结局指标
主要结局
Number of Participants With an Overall Response
时间窗: 6 cycles of treatment (28 days per cycle)
Overall (OR) is the total number of participants with any response: Complete remission (CR), is defined as \> 30% lymphocytes in the bone marrow, recovery of blood counts and no clinical symptoms; Nodular partial remission (NPR), is the same as CR but with nodules; Partial remission (PR) is \> 50% decrease of clinical symptoms from baseline and recovery from blood counts.
次要结局
未报告次要终点