Antibody Therapy With Alemtuzumab, Rituximab and GM-CSF for Initial Treatment of High Risk Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 33
- 试验地点
- 2
- 主要终点
- Number of Confirmed Responses (Complete or Partial Response Noted as the Objective Status for a Duration of at Least 2 Months) at 6 Months
研究概览
简要总结
RATIONALE: 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 find cancer cells and help kill them or carry cancer-killing substances to them. Colony-stimulating factors, such as GM-CSF, may increase the number of immune cells found in bone marrow or peripheral blood. Giving monoclonal antibody therapy together with GM-CSF may be an effective treatment for early-stage chronic lymphocytic leukemia.
PURPOSE: This phase II trial is studying the side effects of giving rituximab and alemtuzumab together with GM-CSF and to see how well it works in treating patients with early-stage chronic lymphocytic leukemia.
详细描述
OBJECTIVES:
Primary
- To assess the rate of complete and overall response in patients with high-risk, early-stage, chronic lymphocytic leukemia (CLL) treated with alemtuzumab, rituximab, and sargramostim (GM-CSF).
- To monitor and assess toxicity of this regimen in these patients through clinical evaluation and serial monitoring of cytomegalovirus antigenemia by polymerase chain reaction (PCR).
Secondary
- To determine the overall and progression-free survival, time to response, time to next treatment, and duration of response in patients treated with this regimen.
- To assess the correlation between individual prognostic markers (i.e., 17p-, 11q-, unmutated VH gene, use of VH3-21, ZAP70+, CD38+) and clinical outcome.
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 120 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •DISEASE CHARACTERISTICS:
- •Diagnosis of chronic lymphocytic leukemia (CLL) meeting the following criteria:
- •Minimum threshold peripheral blood lymphocyte count 5 x 10^9/L
- •Monoclonality (light chain exclusion) of B lymphocytes detected by immunophenotyping (CD19-positive), demonstrating ≥ 3 of the following characteristics:
- •CD5-positive
- •CD23-positive
- •Dim surface light chain expression
- •Dim surface CD20 expression
- •Negative for IGH/CCND1 translocation AND/OR immunostaining is negative for cyclin D1 expression by fluorescent in-situ hybridization (FISH) analysis
- •Rai stage 0, I, or II disease that does not meet standard NCI-Working Group criteria for treatment of CLL
- •Poor prognosis as defined by ≥ 1 of the following factors:
- •Unmutated IgVH mutation status AND CD38 expression (i.e., ≥ 30% cells positive on flow cytometry)
- •Unmutated IgVH mutation status AND ZAP-70 expression (i.e., ≥ 20% cells positive on flow cytometry)
- •VH3-21 gene segment use irrespective of mutation status AND CD38 expression (≥ 30% cells positive on flow cytometry)
- •VH3-21 gene segment use irrespective of mutation status AND ZAP-70 expression (≥ 20% cells positive on flow cytometry)
- •11q-negative*
- •17p-negative* NOTE: *Determination of IgVH mutation status is not required in patients whose eligibility is based on 17p13- or 11q22- deletions
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0- 2
- •Creatinine ≤ 1.5 times upper limit of normal (ULN)
- •Total bilirubin ≤ 3.0 times ULN OR direct bilirubin ≤ 1.5 ULN
- •AST ≤ 3.0 times ULN (unless due to hemolysis or CLL)
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must practice effective contraception
- •Willing to provide mandatory blood samples (for patients at the Mayo Clinic in Rochester only) for research studies as required by the protocol
- •No comorbid conditions, including any of the following:
- •New York Heart Association Class III or IV heart disease
- •Myocardial infarction within the past month
- •Uncontrolled infection
- •HIV infection or AIDS
- •Serological evidence of active hepatitis B infection (i.e., serum antigen or e-antigen positivity) or positive hepatitis C serology
- •No other active primary malignancy requiring treatment or limiting survival to ≤ 2 years
- •No active autoimmune hemolytic anemia, immune thrombocytopenia, or pure red blood cell aplasia
- •PRIOR CONCURRENT THERAPY:
- •More than 4 weeks since prior major surgery
- •No prior chemotherapy or monoclonal antibody treatment for CLL
- •No concurrent corticosteroids
排除标准
- 未提供
研究组 & 干预措施
Alemtuzumab + Rituximab + GM-CSF
Alemtuzumab + Rituximab + GM-CSF
干预措施: Sargramostim (Biological)
Alemtuzumab + Rituximab + GM-CSF
Alemtuzumab + Rituximab + GM-CSF
干预措施: Rituximab (Biological)
Alemtuzumab + Rituximab + GM-CSF
Alemtuzumab + Rituximab + GM-CSF
干预措施: Alemtuzumab (Biological)
结局指标
主要结局
Number of Confirmed Responses (Complete or Partial Response Noted as the Objective Status for a Duration of at Least 2 Months) at 6 Months
时间窗: 6 months
Response, as defined by the National Cancer Institute Working Group (NCIWG), requires the following for a period of at least 2 months: * CR: no lymphadenopathy, hepatomegaly, splenomegaly or constitutional symptoms; normal complete blood count; confirmed by bone marrow (BM) aspirate \& biopsy * PR: 50% decrease in peripheral blood lymphocytes, lymphadenopathy, liver/spleen size, presence/absence of constitutional symptoms; plus ≥1 of the following: ≥1500/μL polymorphonuclear leukocytes, \>100,000/μL platelets, \>11.0 g/dL hemoglobin or 50% improvement for these parameters without transfusions
次要结局
- Time to Next Treatment(time from end of protocol treatment to subsequent treatment (up to 5 years))
- Progression Free Survival(Time from registration to progression (up to 5 years))
- Overall Survival(Time from registration to death (up to 5 years))
- Duration of Response(time from start of response to progression (up to 5 years))