A Phase II Study of Fludarabine + Rituximab Induction Followed by Alemtuzumab (Campath-1H, NSC #715969, IND #10864) Administered Subcutaneously as Consolidation in Untreated Patients With B-Cell Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 102
- 试验地点
- 2
- 主要终点
- Number of Participants With a Complete Response After Treatment With Fludarabine & Rituximab Followed by Alemtuzumab
研究概览
简要总结
This phase II trial is studying how well giving fludarabine together with rituximab followed by alemtuzumab works in treating patients with chronic lymphocytic leukemia. Monoclonal antibodies, such as rituximab and alemtuzumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others can find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy, such as fludarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving fludarabine together with rituximab followed by alemtuzumab may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the rate of complete response and toxicity of concurrent treatment with fludarabine and rituximab followed by consolidative alemtuzumab in patients with previously untreated, but symptomatic, CLL.
II. To determine if alemtuzumab improves the CR rate with acceptable toxicity when administered as consolidation therapy following induction therapy with fludarabine and rituximab.
III. To estimate the progression-free and overall survival of high risk (VH gene unmutated and those with p53 dysfunction) and low-risk (others) patients following therapy with fludarabine and rituximab induction and consolidative alemtuzumab.
IV. To determine the frequency of molecular (PCR) remission following fludarabine and rituximab induction therapy and alemtuzumab consolidation therapy and if this serves as a surrogate marker for prolonged progression-free and overall survival.
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
- •Specific Diagnosis of B-Cell CLL
- •An absolute lymphocytosis of > 5,000/μL
- •Morphologically, the lymphocytes must appear mature with < 55% prolymphocytes
- •Bone marrow examination must include at least a unilateral aspirate and biopsy; the aspirate smear must show > 30% of all nucleated cells to be lymphoid or the bone marrow core biopsy must show lymphoid infiltrates compatible with marrow involvement by CLL; the overall cellularity must be normocellular or hypercellular
- •Local institution lymphocyte phenotype must reveal a predominant B-cell monoclonal population sharing a B-cell marker (CD19, CD20, CD23) with the CD5 antigen, in the absence of other pan-T-cell markers; additionally, the B-cells must be monoclonal with regard to expression of either κ or λ and have surface immunoglobulin expression of low density; patients with bright surface immunoglobulin levels must have CD23 co-expression
- •Patients must be in the intermediate- or high-risk categories of the modified three-stage Rai staging system (i.e., stages I, II, III, or IV)
- •Patients in the intermediate-risk group must have evidence of active disease as demonstrated by at least one of the following criteria:
- •Massive or progressive splenomegaly, hepatomegaly and/or lymphadenopathy;
- •Presence of weight loss > 10% over the preceding 6 month period;
- •Grade 2 or 3 fatigue;
- •Fevers > 100.5°F or night sweats for greater than 2 weeks without evidence of infection;
- •Progressive lymphocytosis with an increase of > 50% over a 2 month period or an anticipated doubling time of less than 6 months
- •No prior therapy for CLL including corticosteroids for autoimmune complications that have developed since the initial diagnosis of CLL
- •No medical condition requiring chronic use of oral corticosteroids
- •Performance Status 0 - 2
- •Due to alterations in host immunity, patients with HIV may not be enrolled
- •Due to the unknown teratogenic potential of alemtuzumab, pregnant or nursing women may not be enrolled; women and men of reproductive potential should agree to use an effective means of birth control
- •Creatinine =< 1.5 x upper limit of institutional normal value
- •Coomb's Testing NEGATIVE
排除标准
- 未提供
研究组 & 干预措施
Treatment (alemtuzumab, rituximab, fludarabine phosphate)
Patients receive induction therapy comprising rituximab IV over 4 hours on days 1, 3, and 5 of course 1 and day 1 of all subsequent courses and fludarabine IV over 30 minutes on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression.
Approximately 4 months after completion of induction therapy, patients achieving a partial response, nodular partial response, or stable disease receive consolidation therapy comprising alemtuzumab subcutaneously on days 1-3. Treatment repeats weekly for up to 6 courses in the absence of disease progression.
干预措施: alemtuzumab (Biological)
Treatment (alemtuzumab, rituximab, fludarabine phosphate)
Patients receive induction therapy comprising rituximab IV over 4 hours on days 1, 3, and 5 of course 1 and day 1 of all subsequent courses and fludarabine IV over 30 minutes on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression.
Approximately 4 months after completion of induction therapy, patients achieving a partial response, nodular partial response, or stable disease receive consolidation therapy comprising alemtuzumab subcutaneously on days 1-3. Treatment repeats weekly for up to 6 courses in the absence of disease progression.
干预措施: rituximab (Biological)
Treatment (alemtuzumab, rituximab, fludarabine phosphate)
Patients receive induction therapy comprising rituximab IV over 4 hours on days 1, 3, and 5 of course 1 and day 1 of all subsequent courses and fludarabine IV over 30 minutes on days 1-5. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression.
Approximately 4 months after completion of induction therapy, patients achieving a partial response, nodular partial response, or stable disease receive consolidation therapy comprising alemtuzumab subcutaneously on days 1-3. Treatment repeats weekly for up to 6 courses in the absence of disease progression.
干预措施: fludarabine phosphate (Drug)
结局指标
主要结局
Number of Participants With a Complete Response After Treatment With Fludarabine & Rituximab Followed by Alemtuzumab
时间窗: Duration of treatment (up to 13.5 months)
A complete response, as defined by the National Cancer Institute Working Group (NCIWG): - CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy
次要结局
- 2 Year Progression Free Survival(2 years from registration)
- Number of Participants With Severe Non-Hematologic Adverse Events During Treatment With Alemtuzumab(6 weeks beginning at study week 36)
- Number of Participants With a Complete or Partial Response After Induction Therapy With Fludarabine & Rituximab(Up to 9 months)
- 2 Year Survival(2 years from registration)