A Multi-Center Phase 2 Efficacy and Pharmacokinetic Study Evaluating Fludarabine, Cyclophosphamide, and Subcutaneous Campath (FCCam, Alemtuzumab) for Previously Untreated B-Cell Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Number of Subjects Maintaining Partial Response (PR) or Complete Response (CR)
研究概览
简要总结
The primary objective of this study was to evaluate the safety and efficacy of the combination of fludarabine and cyclophosphamide in previously untreated CLL patients. Participants will receive fludarabine and cyclophosphamide on days 1, 2, and 3 of six 28-day cycles.
详细描述
This single-arm study evaluated the safety and efficacy of the combination of fludarabine 25 mg/m2/d IV and cyclophosphamide 250 mg/m2/d SC in previously untreated CLL patients. Participants received fludarabine and cyclophosphamide on days 1, 2, and 3 of six 28-day cycles, followed by a no-treatment rest period (observation) for 3 to 12 weeks.
Responders entered a no-treatment rest period (observation) for 3 to 8 weeks, then depending on status, continued on follow-up or on-study to receive Campath stating at 3 mg/day with the dose adjusted to the maximum tolerated dose.
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
- •Karnofsky performance status 60% or above
- •Confirmed immunohistological diagnosis of Chronic Lymphocytic Leukemia (CLL)
- •Rai Stage I to IV as follows:
- •Advanced stage disease (Rai Stage III or IV, or modified Rai High Risk)
- •Patients with Rai Stage I - II or (Modified Rai Intermediate-Risk) disease must have an indication for therapy based on 1996 NCI revised criteria for active disease as follows:
- •Any one of the following disease-related symptoms:
- •Weight loss ≥ 10% body weight within the previous 6 months
- •Extreme fatigue
- •Fever greater than 100.5° F for ≥ 2 weeks without evidence of infection
- •Night sweats without evidence of infection
- •Evidence of progressive marrow failure based on the development of worsening of anemia or thrombocytopenia
- •Autoimmune anemia and/or thrombocytopenia poorly responsive to corticosteroid therapy
- •Massive (> 6 cm below the left costal margin) or progressive splenomegaly
- •Bulky (>10 cm in cluster) or progressive lymphadenopathy
- •Progressive lymphocytosis > 50% increase over 2 months, or anticipated doubling time < 6 months
- •Patients with immunoglobulin VH gene in unmutated nucleotide sequence configuration, as defined by ≥ 98% homology with the nearest germline counterpart
- •Serum creatinine ≤ 2x the upper limit of normal
- •Total serum bilirubin ≤ 2x the upper limit of normal.
- •AST ≤ 2x the upper limit of normal.
- •ALT ≤ 2x the upper limit of normal.
- •Signed written informed consent
排除标准
- •Prior pharmacological treatment for CLL
- •Past history of anaphylaxis following exposure to monoclonal antibodies
- •Active secondary malignancy or a history of malignant disease (other than CLL or non-melanoma skin cancer) within the preceding 5 years
- •Any medical condition requiring systemic corticosteroids
- •Active systemic infection
- •Major systemic or other illness (including Coombs positivity and active hemolysis) that would, in the opinion of the investigator, interfere with the patient's ability to comply with the protocol, compromise patient safety, or interfere with the interpretation of study results
- •HIV positive by serologic testing
- •Pregnant or nursing female
- •Unwilling/unable to practice an acceptable form of contraception.
研究组 & 干预措施
Fludarabine, cytoxan, then alemtuzumab
Fludarabine and cyclophosphamide days 1 to 3 for six 28-day cycles. Minimal residual disease positive responders continued on-treatment to receive alemtuzumab 30 mg weekly. MRD negative responders were observed.
干预措施: Alemtuzumab (Drug)
Fludarabine, cytoxan, then alemtuzumab
Fludarabine and cyclophosphamide days 1 to 3 for six 28-day cycles. Minimal residual disease positive responders continued on-treatment to receive alemtuzumab 30 mg weekly. MRD negative responders were observed.
干预措施: Fludarabine (Drug)
Fludarabine, cytoxan, then alemtuzumab
Fludarabine and cyclophosphamide days 1 to 3 for six 28-day cycles. Minimal residual disease positive responders continued on-treatment to receive alemtuzumab 30 mg weekly. MRD negative responders were observed.
干预措施: Cytoxan (Drug)
结局指标
主要结局
Number of Subjects Maintaining Partial Response (PR) or Complete Response (CR)
时间窗: 24 weeks
Response criteria as per the NCI-WG Revised Guidelines for B-CLL Complete remission: No lymphadenopathy by physical exam No hepatomegaly or splenomegaly Absence of constitutional symptoms Polymorphonuclear leukocytes \> 1,500/uL, Platelets \> 100,000/uL, Hemoglobin \> 11.0 g/dL Bone marrow aspirate and biopsy normocellular with \< 30% lymphocytes Absent lymphoid nodules Partial remission: * 50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value * 50% reduction in lymphadenopathy and/or ≥ 50% reduction in the size of the liver and/or spleen AND one or more of the following Polymorphonuclear leukocytes \> 1,500/uL or 50% improvement over baseline Platelets \> 100,000/uL or 50% improvement over baseline Hemoglobin \> 11.0 g/dL or 50% improvement over baseline
次要结局
- Duration of Response(105 months)
研究者
Steven E. Coutre
Associate Professor of Medicine
Stanford University