Fludarabine, Cyclophosphamide, and Rituximab (FCR) Plus Sargramostim (GM-CSF) as Frontline Therapy for Symptomatic Chronic Lymphocytic Leukemia
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
- Participant Overall Response Rate (ORR) at 6 Months Includes Complete Remissions, Partial Remission, or Nodule Partial Remissions.
研究概览
简要总结
The goal of this clinical research study is to learn if using a combination of fludarabine, cyclophosphamide, and rituximab, with sargramostim (GM-CSF) can help to control previously untreated chronic lymphocytic leukemia (CLL). The safety of this combination will also be studied. This study will evaluate antibody-dependent cellular cytotoxicity (ADCC) and its relationship to response.
详细描述
Fludarabine and cyclophosphamide are designed to enter CLL cells and destroy the "machinery" that allows CLL cells to multiply. Rituximab is designed to bind to CLL cells and cause cell death. GM-CSF is designed to help the bone marrow to produce white cells. It may also increase the target molecule called cluster of differentiation antigen 20 (CD20) for rituximab on the surface of the CLL cells which may improve the activity of rituximab.
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. Blood (about 2 tablespoons) will be drawn for routine tests. The routine blood draw will include a test for hepatitis B, unless this has been done within the last 6 months. This routine blood draw will also include a pregnancy test for women who are able to have children. To be eligible to take part in this study, the pregnancy test must be negative. A bone marrow aspirate and biopsy will be collected. To collect a bone marrow aspirate and biopsy, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow and bone is withdrawn through a large needle.
If you are found to be eligible to take part in the study, you will receive GM-CSF thorough a needle under your skin on Day 1. Each study cycle is about 4 weeks, but may be longer depending on side effects or leukemia response.
You will receive rituximab through a needle in your vein on Day 2. The first infusion may take up to 8 hours. For every dose of rituximab after that, the infusion may take 2-4 hours. The length of the infusion time depends on whether you have any reactions to the infusion. The dose level of rituximab may be increased for Cycles 2-6 as well. The drugs Tylenol (acetaminophen) and Benadryl (diphenhydramine hydrochloride) will be given before each dose of rituximab. This will be done to decrease the risk of side effects. If side effects do occur during rituximab treatment, the drug may have to be stopped until the side effects go away and then restarted, so your time in the outpatient area may be longer if that occurs.
On Days 3-5 of the first treatment cycle, fludarabine and cyclophosphamide will be given through a needle in your vein. Each infusion will take about 30 minutes. After the first treatment cycle, fludarabine and cyclophosphamide will be given on Days 2, 3, and 4 for every cycle after that.
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
- •Untreated CLL, CLL/PLL, or SLL (small lymphocytic lymphoma) with indication for therapy. Indications for therapy include at least one of the following: (1) one or more disease-related symptoms [fever, night sweats, weight loss > 10% in prior 6 months, pronounced fatigue]; (2) advanced stage disease (Rai stage >/= 3 or Binet stage C); (3) autoimmune anemia and/or thrombocytopenia that is unresponsive to other therapies; (4) massive or progressive hepatomegaly and/or splenomegaly and/or lymphadenopathy; (5) recurrent infections; (6) rapid lymphocyte doubling time of < 6 months.
- •Patients who have been treated with not more than one regimen of immunotherapy (e.g. rituximab, alemtuzumab, rituximab plus alemtuzumab) for a diagnosis of CLL, CLL/PLL, or SLL (small lymphocytic lymphoma).
- •Beta-2-microglobulin </= 4 mg/dL.
- •Adequate liver function (total bilirubin </= 2.5 mg/dL, serum glutamate pyruvate transaminase (SGPT) </=4 x ULN) and renal function (serum creatinine </= 2.0 mg/dL and/or creatinine clearance < 30 mL/hour). Patients with renal or liver dysfunction due to suspected organ infiltration by lymphocytes may be eligible after discussion with the Principal Investigator, but upper limits for creatinine even under these circumstances must be creatinine < 3mg/dL and bilirubin < 6 mg/dL. Patients with Gilbert's syndrome may be entered on study with bilirubin levels </= 4 mg/dL.
- •Eastern Cooperative Oncology Group (ECOG) performance status </=
- •Signed informed consent in keeping with the policies of the hospital.
- •Male and female patients who are fertile agree to use an effective barrier method of birth control (ie, latex condom, diaphragm, cervical cap, etc) to avoid pregnancy. Female patients of childbearing potential (non-childbearing is defined as >/= 1 year after menses cease and/or surgically sterilized) need a negative serum or urine pregnancy test within 2 days of study enrollment..
排除标准
- •Active hepatitis B (at least one of the following markers positive: HBsAg, hepatitis B e antigen (HBeAg), immunoglobulin M (IgM) anti-HBc, hepatitis B virus (HBV) DNA).
- •Concurrent chemotherapy or immunotherapy.
- •Pregnant patients.
- •History of HIV
- •Symptomatic central nervous system (CNS) disease
研究组 & 干预措施
FCR + Sargramostim
Fludarabine + Cyclophosphamide + Rituximab (FCR) = Fludarabine - Course 1: 25 mg/m^2 IV Days 2-4; Course 2-6: 25 mg/m^2 IV Days 1-3. Cyclophosphamide - Course 1: 250 mg/m^2 intravenous (IV) Days 2-4; Course 2-6: 250 mg/m^2 Days 1-3. Rituximab - Course 1: 375 mg/m^2 IV over 2-6 hours Day 1; Course 2-6: 500 mg/m^2 IV Day 1. Sargramostim - Course 1: 250 mcg/m^2 subcutaneous (SQ) Days -1 and 5-11; Course 2-6: 250 mcg/m^2 SQ Days -1 and 4-10.
干预措施: Cyclophosphamide (Drug)
FCR + Sargramostim
Fludarabine + Cyclophosphamide + Rituximab (FCR) = Fludarabine - Course 1: 25 mg/m^2 IV Days 2-4; Course 2-6: 25 mg/m^2 IV Days 1-3. Cyclophosphamide - Course 1: 250 mg/m^2 intravenous (IV) Days 2-4; Course 2-6: 250 mg/m^2 Days 1-3. Rituximab - Course 1: 375 mg/m^2 IV over 2-6 hours Day 1; Course 2-6: 500 mg/m^2 IV Day 1. Sargramostim - Course 1: 250 mcg/m^2 subcutaneous (SQ) Days -1 and 5-11; Course 2-6: 250 mcg/m^2 SQ Days -1 and 4-10.
干预措施: Fludarabine (Drug)
FCR + Sargramostim
Fludarabine + Cyclophosphamide + Rituximab (FCR) = Fludarabine - Course 1: 25 mg/m^2 IV Days 2-4; Course 2-6: 25 mg/m^2 IV Days 1-3. Cyclophosphamide - Course 1: 250 mg/m^2 intravenous (IV) Days 2-4; Course 2-6: 250 mg/m^2 Days 1-3. Rituximab - Course 1: 375 mg/m^2 IV over 2-6 hours Day 1; Course 2-6: 500 mg/m^2 IV Day 1. Sargramostim - Course 1: 250 mcg/m^2 subcutaneous (SQ) Days -1 and 5-11; Course 2-6: 250 mcg/m^2 SQ Days -1 and 4-10.
干预措施: Sargramostim (Drug)
FCR + Sargramostim
Fludarabine + Cyclophosphamide + Rituximab (FCR) = Fludarabine - Course 1: 25 mg/m^2 IV Days 2-4; Course 2-6: 25 mg/m^2 IV Days 1-3. Cyclophosphamide - Course 1: 250 mg/m^2 intravenous (IV) Days 2-4; Course 2-6: 250 mg/m^2 Days 1-3. Rituximab - Course 1: 375 mg/m^2 IV over 2-6 hours Day 1; Course 2-6: 500 mg/m^2 IV Day 1. Sargramostim - Course 1: 250 mcg/m^2 subcutaneous (SQ) Days -1 and 5-11; Course 2-6: 250 mcg/m^2 SQ Days -1 and 4-10.
干预措施: Rituximab (Drug)
结局指标
主要结局
Participant Overall Response Rate (ORR) at 6 Months Includes Complete Remissions, Partial Remission, or Nodule Partial Remissions.
时间窗: Baseline to 6 Months
Complete Remission:Normal exam/No symptoms; Absolute lymphocyte count (ALC)\</=4x10\^9/L, Hb\>11 g/dL, absolute neutrophil count (ANC)\>/=1.5x109/L, \& platelet count\>100x109/L. Bone marrow:\<30% lymphocytes aspirate no biopsy evidence disease; Disappearance palpable lymph nodes/spleen/liver, no new lesions. Partial Remission:ALC reduced 50%,either Hb\>11 g/dL or 50% improvement (imp.) in deviation, or ANC\>/=1.5x109/L or 50% imp., or platelet\>100x109/L or 50% imp. in deviation from normal. Reduced 50% palpable lymph nodes/spleen/liver no new lesions. Nodular Partial Response:ALC\</=4x109/L + Hb\>11 g/dL, ANC\>/=1.5x109/L \& platelet count\>100x109/L; \<30% lymphocytes - bone marrow biopsy aspirate + lymphoid nodules;No palpable lymph nodes/spleen/liver tumors without new lesions. Progressive Disease:50% increase (incr.) ALC\>10x109/L twice; tumor lesion incr. 50% over entry or responder size at time max regression \&/or appearance new malignant disease; Reappearance bone marrow disease.
Number of Participants With Overall Response Includes Complete Remissions, Partial Remission, or Nodule Partial Remissions.
时间窗: Baseline to 6 Months
Complete Remission:Normal exam/No symptoms; Absolute lymphocyte count (ALC)\</=4x10\^9/L, Hb\>11 g/dL, absolute neutrophil count (ANC)\>/=1.5x109/L, \& platelet count\>100x109/L. Bone marrow:\<30% lymphocytes aspirate no biopsy evidence disease; Disappearance palpable lymph nodes/spleen/liver, no new lesions. Partial Remission:ALC reduced 50%,either Hb\>11 g/dL or 50% improvement (imp.) in deviation, or ANC\>/=1.5x109/L or 50% imp., or platelet\>100x109/L or 50% imp. in deviation from normal. Reduced 50% palpable lymph nodes/spleen/liver no new lesions. Nodular Partial Response:ALC\</=4x109/L + Hb\>11 g/dL, ANC\>/=1.5x109/L \& platelet count\>100x109/L; \<30% lymphocytes - bone marrow biopsy aspirate + lymphoid nodules;No palpable lymph nodes/spleen/liver tumors without new lesions. Progressive Disease:50% increase (incr.) ALC\>10x109/L twice; tumor lesion incr. 50% over entry or responder size at time max regression \&/or appearance new malignant disease; Reappearance bone marrow disease.
次要结局
- Number of Participants Progression-free(6 months or until disease progression if earlier)