Phase II Randomized Trial of Early Versus Late Vaccination in Patients With High Risk CLL
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- Efficacy and toxicity
研究概览
简要总结
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as rituximab, 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. Vaccines may help the body build an effective immune response to kill cancer cells. Giving cyclophosphamide and rituximab together with vaccine therapy may kill more cancer cells.
PURPOSE: This randomized phase II trial is studying cyclophosphamide and rituximab followed by two different schedules of vaccine therapy to compare how well they work in treating patients with chronic lymphocytic leukemia.
详细描述
OBJECTIVES:
- Determine the efficacy and toxicity of cyclophosphamide and rituximab in patients with previously untreated, high-risk chronic lymphocytic leukemia.
- Determine, preliminarily, the efficacy and toxicity of early vs delayed administration of vaccine therapy comprising KGEL and autologous tumor cells after cyclophosphamide and rituximab in these patients.
- Compare the magnitude of the T-cell response to early vs delayed administration of this vaccine after rituximab and cyclophosphamide and correlate these responses with the extent of immune reconstruction.
OUTLINE: This is a randomized phase II study for patients with asymptomatic or minimally symptomatic, untreated CLL with poor-risk features.
Patients undergo peripheral blood collection for vaccine production. Patients then receive rituximab IV over at least 4 hours on days 1 and 2 in course 1 and on day 1 only in subsequent courses and cyclophosphamide IV over 1 hour on day 1. Treatment with rituximab and cyclophosphamide repeats every 21 days for up to 6 cycles in the absence of disease progression. Patients undergo evaluation 4 weeks after completion of rituximab and cyclophosphamide. Patients achieving partial or complete response are randomized to 1 of 2 vaccine treatment arms.
- Arm I (early administration): Beginning 2 weeks after evaluation, patients receive vaccine therapy comprising an autologous tumor admixed with an allogeneic vaccine (KGEL) that produces sargramostim (GM-CSF) and autologous tumor cells intradermally. Treatment repeats every 3 weeks for 6 courses in the absence of unacceptable toxicity.
- Arm II (late administration): Beginning 20 weeks after evaluation, patients receive vaccine therapy comprising KGEL and autologous tumor cells intradermally. Treatment repeats every 3 weeks for 6 courses in the absence of unacceptable toxicity.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 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
- •DISEASE CHARACTERISTICS:
- •Diagnosis of chronic lymphocytic leukemia (CLL)
- •Meets 1 of the following high-risk features:
- •17p deletion by fluorescent in situ hybridization (FISH)
- •11q deletion by FISH
- •Unmutated immunoglobulin heavy chain variable region (IgVH) genes, defined as ≥ 98% homology with germline in a Clinical Laboratory Improvement Act (CLIA) approved laboratory
- •Any stage disease
- •Previously untreated disease
- •Not requiring immediate treatment
- •Absolute lymphocyte count ≥ 20,000/mm³
- •PATIENT CHARACTERISTICS:
- •ECOG performance status 0-2
- •Creatinine ≤ 2.0 mg/dL
- •Bilirubin ≤ 2 mg/dL (unless secondary to obstructive cholestasis from lymphadenopathy or Gilbert's disease)
- •Not pregnant or nursing
- •Negative pregnancy test
- •Fertile patients must use effective contraception
- •No active infections requiring oral or intravenous antibiotics
- •No autoimmune disorder (e.g., autoimmune hemolytic anemia) requiring corticosteroids before the start of study vaccination
- •No other malignancy except nonbasal cell skin cancer, carcinoma in situ of the cervix, or tumor that was treated with curative intent ≥ 2 years ago
- •PRIOR CONCURRENT THERAPY:
- •No prior therapy for CLL
排除标准
- 未提供
结局指标
主要结局
Efficacy and toxicity
T-cell response to early versus late vaccine therapy comprising KGEL and autologous tumor cells
次要结局
未报告次要终点