A Phase II Study of Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) in High-Risk Previously Untreated Patients With CLL
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Overall Participant Response
研究概览
简要总结
Primary Objective:
- Evaluate the ability of Cyclophosphamide, Fludarabine, Alemtuzumab, and Rituximab (CFAR) to increase the proportion of patients with <5% CD5/CD19+ cells in bone marrow to 66% following 3 courses of treatment without significantly increasing the incidence of pneumonia or sepsis compared to a historic group of patients treated with the combination fludarabine, cyclophosphamide, and rituximab (FCR).
Second Objectives:
- Assess complete remission (CR), nodular partial remission (nPR), and partial remission (PR) rates (overall response) in high-risk, previously untreated patients with CLL treated with CFAR.
- Evaluate molecular remission in bone marrow by polymerase chain reaction (PCR) for the clonal immunoglobulin heavy chain variable gene in responders treated with CFAR.
- Assess immune parameters including blood T cell counts and subset distribution and serum immunoglobulin levels pretreatment, during treatment, and post-treatment in patients treated with CFAR.
详细描述
Fludarabine is a chemotherapy drug that is approved for the treatment of patients with Chronic Lymphocytic Leukemia (CLL). Cyclophosphamide is also a chemotherapy drug that is commonly used to treat patients with CLL. Rituximab and alemtuzumab are special proteins (antibodies) that specifically target and attach to proteins on leukemia cells. These targeted proteins may also be present on normal blood cells. When these antibodies 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 previously untreated patients with CLL. The purpose of this study is to see if there is added benefit with the addition of alemtuzumab to this combination.
Before you can start treatment on this study, you will have what are called "screening tests." These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete physical exam, including routine blood tests (about 3 tablespoons). You may have either a chest x-ray or a computerized tomography (CT) scan if your doctor thinks it is necessary. If you have not had a bone marrow biopsy collected in the past 4 months, you will have a bone marrow sample collected at this time. To collect a bone marrow biopsy, 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 or urine pregnancy test.
If you are found to be eligible to take part in this study, you may begin treatment. During this 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 3 and a half 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 premedication and fluids by vein to help decrease the risk of side effects. The premedication may include steroids that are used to decrease the risk of side effects from the alemtuzumab and rituximab. They will be given before each dose of the alemtuzumab and rituximab. The infusions for each daily treatment visit should take less than 6 hours. This treatment will be given on an outpatient basis. The combination treatment will be repeated every 4 weeks (1 cycle) for a total of up to 6 cycles.
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 the first dose of alemtuzumab of each cycle. These drugs will be used to help decrease the risk of 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 to be observed, for 2 hours after the drug is given.
During the treatment and for 2 months after completion of treatment, you will need to take antibiotics to decrease the risk of developing infection.
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
- — 至 69 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •All patients must have a diagnosis of CLL by immunophenotyping and flow cytometry analysis of blood or bone marrow and be previously untreated.
- •All patients must be younger than 70 years and have a serum beta-2 microglobulin of >/= 4.0mg/L.
- •All patients with Rai stage III-IV are eligible for treatment on 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 on 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), Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF), etc.
- •Patients must not have untreated or uncontrolled life-threatening infection.
- •Patients must sign informed consent.
排除标准
- •Patients older than 70 years.
研究组 & 干预措施
CFAR
CFAR = Cyclophosphamide 200 mg/m^2/day 3-5 intravenous (IV) 5-30 minutes, Fludarabine 20 mg/m^2/day 3-5 IV 5-30 minutes, Alemtuzumab 30 mg 1, 3,5 IV 2-4 hours, and Rituximab 375 mg/m^2/day 2 IV 4-6 hours
干预措施: Cyclophosphamide (Drug)
CFAR
CFAR = Cyclophosphamide 200 mg/m^2/day 3-5 intravenous (IV) 5-30 minutes, Fludarabine 20 mg/m^2/day 3-5 IV 5-30 minutes, Alemtuzumab 30 mg 1, 3,5 IV 2-4 hours, and Rituximab 375 mg/m^2/day 2 IV 4-6 hours
干预措施: Fludarabine (Drug)
CFAR
CFAR = Cyclophosphamide 200 mg/m^2/day 3-5 intravenous (IV) 5-30 minutes, Fludarabine 20 mg/m^2/day 3-5 IV 5-30 minutes, Alemtuzumab 30 mg 1, 3,5 IV 2-4 hours, and Rituximab 375 mg/m^2/day 2 IV 4-6 hours
干预措施: Alemtuzumab (Drug)
CFAR
CFAR = Cyclophosphamide 200 mg/m^2/day 3-5 intravenous (IV) 5-30 minutes, Fludarabine 20 mg/m^2/day 3-5 IV 5-30 minutes, Alemtuzumab 30 mg 1, 3,5 IV 2-4 hours, and Rituximab 375 mg/m^2/day 2 IV 4-6 hours
干预措施: Rituximab (Drug)
结局指标
主要结局
Overall Participant Response
时间窗: Evaluated after 3 courses of 4 week therapy (12 weeks)
Overall Response: Complete remission (CR), nodular partial remission (nPR), and partial remission (PR) rates (overall response) in high-risk, previously untreated patients with CLL treated with CFAR. National Cancer Institute - Working Group (NCI-WG) response criteria. CR defined as zero nodes, Liver/spleen not palpable, zero symptoms, polymorphonuclear leukocyte (PMN)\>1,500/uL, Platelets \>100,000uL, Hemoglobin (untransfused) \>11.0g/dL, Lymphocytes \<4,000/uL and Bone Marrow Aspirate biopsy \<30% lymphocytes with no lymphocyte infiltrate; PR defined as nodes \>/= 50% decrease,Liver/spleen \>/= 50% decrease, symptoms not applicable, PMN \>1,500/uL or \>50% improvement from baseline, Platelets 100,000uL or \>/=50% decrease improvement from baseline, Hemoglobin (untransfused) \>11.0g/dL or \>50% improvement from baseline, Lymphocytes \>50% decrease and Bone Marrow Aspirate biopsy Not Applicable for PR; with nPR defined same as PR but with \<30% lymphocytes with residual disease on biopsy.
次要结局
未报告次要终点