A Phase I Feasibility Trial of Cyclophosphamide, Alvocidib (Flavopiridol) and Rituximab (CAR) in Patients With High Risk B-cell CLL/SLL
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 9
- 试验地点
- 1
- 主要终点
- Maximum-tolerated dose of combination therapy with Cyclophosphamide, Alvocidib, and Rituximab
研究概览
简要总结
This phase I trial is studying the side effects and the best dose of alvocidib when given together with cyclophosphamide and rituximab in treating patients with high risk B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma. 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. Alvocidib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as rituximab, can also block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Other find cancer cells and help kill them or carry cancer-killing substances to them. Giving cyclophosphamide, alvocidib, and rituximab together may kill more cancer cells.
详细描述
PRIMARY OBJECTIVES:
I. To determine the dose-limiting toxicity and maximum-tolerated dose of treatment with cyclophosphamide, alvocidib, and rituximab in patients with high-risk B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.
II. To determine the feasibility of administering this regimen as an outpatient regimen in these patients.
SECONDARY OBJECTIVES:
I. To determine the complete response rate, partial response rate, and minimal-residual disease-negative response rate in patients treated with this regimen.
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
- •Histologically confirmed chronic lymphocytic leukemia (CLL) or B-cell prolymphocytic leukemia* (PLL) arising from CLL
- •Patients must have documented B-cell lymphocytosis > 5 x 10^9/L at some point since initial diagnosis of CLL
- •Patients must have B-cells that co-express CD5 with CD19 or CD20
- •Patients who do not have dim sIg or CD23 expression on their leukemia cells should be examined for cyclin D1 over-expression or t(11;14) to rule out mantle cell lymphoma
- •To be considered high risk, patients must meet the following criteria:
- •At least 1 of the following:
- •17p deletion
- •11q deletion
- •Un-mutated IgV_H (≥ 98% homology)
- •Age > 70 years
- •B_2M > 4
- •AND at least 1 of the following:
- •Progressive or marked splenomegaly and/or lymphadenopathy
- •Anemia (hemoglobin < 11 g/dL) or thrombocytopenia (platelets < 100,000/mm^3)
- •Weight loss exceeding 10% of body weight over preceding 6 months
- •NCI grade 2 or 3 fatigue
- •Fevers > 100.5° F or night sweats for > 2 weeks without evidence of infection
- •Progressive lymphocytosis, with an increase exceeding 50% over a 2-month period or a doubling time of < 6 months
- •No other concurrent hormones, chemotherapy, or radiotherapy except for steroids for new adrenal failure or hormones for nondisease-related conditions (e.g., insulin for diabetes)
- •No requirement for chronic corticosteroids
- •ECOG performance status 0-2
- •Creatinine ≤ 2.0 mg/dL
- •Bilirubin ≤ 1.5 times normal unless due to Gilbert disease, hemolysis, or disease infiltration of the liver
- •AST ≤ 2 times normal unless due to hemolysis or disease infiltration of the liver
- •Negative pregnancy test
- •Not pregnant or nursing
- •Fertile patients must use effective contraception
- •No secondary or other malignancy that will limit survival to < 2 years
- •No uncontrolled concurrent illness including, but not limited to, any of the following:
- •Ongoing or active infection
- •Symptomatic congestive heart failure
- •Unstable angina pectoris
- •Cardiac arrhythmia
- •Psychiatric illness or social situations that would limit compliance with study requirements
- •No uncompensated HIV without adequate CD4 (> 200/mm^3) and requiring HIV medication
- •No active hepatitis B infection
- •No known G6PD deficiency
- •No history of allergic reactions attributed to compounds of similar chemical or biologic composition to alvocidib, cyclophosphamide, rituximab, or other agents used in this study
- •No prior alvocidib
- •No prior purine analog therapy
- •No more than 1 prior treatment with a biologic or alkylating agent
- •No other concurrent investigational agents
排除标准
- 未提供
研究组 & 干预措施
Treatment (rituximab, cyclophosphamide, alvocidib)
Patients receive rituximab IV over 4 hours on days 1 (days 1-3 in course 1), cyclophosphamide IV over 30-60 minutes on days 1-3, and alvocidib IV over 4.5 hours on days 1 and 8 (day 8 only in course 1).
干预措施: Pharmacological Study (Other)
Treatment (rituximab, cyclophosphamide, alvocidib)
Patients receive rituximab IV over 4 hours on days 1 (days 1-3 in course 1), cyclophosphamide IV over 30-60 minutes on days 1-3, and alvocidib IV over 4.5 hours on days 1 and 8 (day 8 only in course 1).
干预措施: Alvocidib Hydrochloride (Drug)
Treatment (rituximab, cyclophosphamide, alvocidib)
Patients receive rituximab IV over 4 hours on days 1 (days 1-3 in course 1), cyclophosphamide IV over 30-60 minutes on days 1-3, and alvocidib IV over 4.5 hours on days 1 and 8 (day 8 only in course 1).
干预措施: Cyclophosphamide (Drug)
Treatment (rituximab, cyclophosphamide, alvocidib)
Patients receive rituximab IV over 4 hours on days 1 (days 1-3 in course 1), cyclophosphamide IV over 30-60 minutes on days 1-3, and alvocidib IV over 4.5 hours on days 1 and 8 (day 8 only in course 1).
干预措施: Diagnostic Laboratory Biomarker Analysis (Other)
Treatment (rituximab, cyclophosphamide, alvocidib)
Patients receive rituximab IV over 4 hours on days 1 (days 1-3 in course 1), cyclophosphamide IV over 30-60 minutes on days 1-3, and alvocidib IV over 4.5 hours on days 1 and 8 (day 8 only in course 1).
干预措施: Rituximab (Biological)
结局指标
主要结局
Maximum-tolerated dose of combination therapy with Cyclophosphamide, Alvocidib, and Rituximab
时间窗: 21 days
Determined using the CTEP Active Version of the CTCAE.
Treatment related adverse events assessed using the CTEP Active Version of the CTCAE
时间窗: Up to 5 years
次要结局
未报告次要终点