A Phase I-II Study of Oxaliplatin, Fludarabine, Cytarabine and Rituximab in Patients With Richter's Transformation, Prolymphocytic Leukemia or Refractory/Relapsed B-Cell Chronic Lymphocytic Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Maximum Tolerated Dose (MTD) Oxaliplatin
研究概览
简要总结
Primary Objectives:
- Determine the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of oxaliplatin in combination with fludarabine, Ara-C and rituximab in patients with Richter's transformation, prolymphocytic leukemia (PLL), or refractory/relapsed B-cell chronic lymphocytic leukemia (CLL).
- Assess the complete response (CR) and partial response (PR) rate to combination therapy of oxaliplatin, fludarabine, Ara-C and rituximab in patients with Richter's transformation, PLL or refractory/relapsed B-cell CLL.
- Determine the safety and toxicity profile of combination therapy of oxaliplatin, fludarabine, Ara-C and rituximab in patients with Richter's transformation, PLL or refractory/relapsed B-cell CLL.
Secondary Objectives:
- Determine the duration of response, failure-free survival, and overall survival.
- Determine the incidence of infections (bacterial, fungal, and viral) in patients with Richter's transformation, prolymphocytic leukemia or refractory/relapsed B-cell CLL treated with rituximab, oxaliplatin, fludarabine and Ara-C; monitor immune parameters such as T cell counts and immunoglobulin levels; and monitor Epstein-Barr virus (EBV) status.
- Characterize the pharmacodynamics of oxaliplatin in leukemia cells with respect to total adduct formation, cross-link formation and excision deoxyribonucleic acid (DNA) responses. Compare these parameters in cells from the same patient after treatment with oxaliplatin in combination with fludarabine and Ara-C.
详细描述
Oxaliplatin, fludarabine, cytarabine and rituximab are anticancer drugs. Oxaliplatin is a platinum compound that has been shown to be effective in fighting other cancers. Oxaliplatin is a third generation platinum compound with higher activity and less toxicity in colon cancer and other tumors compared to other platinum compounds, such as cisplatin. Oxaliplatin has shown activity in patients with relapsed or refractory non-Hodgkin's lymphoma.
Before treatment starts, you will have a complete physical exam and routine blood tests (about 2 teaspoons). A bone marrow sample will be collected. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. Women who are able to have children must have a negative blood or urine pregnancy test.
This research study has two parts, a Phase I part and a Phase II part. You will receive at least 1 cycle of therapy.
Oxaliplatin will be given through a needle in your vein (called an IV) for 4 days (Days 1 through 4). Rituximab will be given through an IV on Day 3 of the first cycle and on Day 1 on every cycle after that. One day after the first dose of oxaliplatin and rituximab (Day 2), fludarabine and cytarabine will be given through an IV for two days (Days 2 and 3). Peg-filgrastim will be given subcutaneously (through a needle just under your skin) on Day 6. Other IV fluids such as saline will be given on all of the treatment days to keep you from being dehydrated, which means that the daily visit may take eight hours. The combination will be repeated once a cycle (every 28 days) for up to a total of 6 cycles.
During the Phase I and II phases of the study, researchers will be testing different dose levels of the study drug combination. Three patients will be enrolled at each dose level. Each time the dose level is raised, it will occur after each patient has been monitored for 28 days. Individual patients who do not experience serious drug-related side effects after the second cycle may receive the next higher dose level for the following treatment cycles.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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
- •Histologically or cytologically confirmed Richter's transformation, fludarabine-refractory chronic lymphocytic leukemia or prolymphocytic leukemia.
- •Patients must be 18 years of age or older.
- •Patients must have a performance status of 0-2 (Zubrod scale).
- •Patients must have adequate renal function (serum creatinine below or equal to 2mg/dL or creatinine clearance greater than 30mL/min), unless renal dysfunction is considered due to organ infiltration by disease.
- •Patients must have adequate hepatic function (bilirubin less than or equal to 2.0 mg/dl; Serum glutamic oxaloacetic transaminase (SGOT) or serum glutamic pyruvic transaminase (SGPT) less than or equal to 3 times the upper limit of normal (ULN) for the reference lab unless considered due to leukemia or congenital hemolytic disorder (for bilirubin).
- •Female patients of childbearing potential (including those <1 year post-menopausal) and male patients must agree to use contraception.
- •Patients must sign an informed consent indicating that they are aware of the investigational nature of this study in keeping with the policies of the hospital.
- •Patients must have platelet counts greater or equal to 20,000, unless due to disease involvement, or autoimmune disorders.
排除标准
- •Untreated or uncontrolled life-threatening infection.
- •Oxaliplatin, fludarabine, cytarabine or rituximab intolerance.
- •Pregnancy or lactation.
- •Chemotherapy and/or radiation therapy within 4 weeks.
- •Medical condition, including mental illness or substance abuse, deemed by the Investigator to be likely to interfere with a patient's ability to sign informed consent, cooperate and participate in the study, or interfere with the interpretation of the results.
研究组 & 干预措施
Oxaliplatin, Fludarabine, Cytarabine + Rituximab
Starting dose oxaliplatin 17.5mg/m^2/day intravenous (IV) for 4 days; Fludarabine 30 mg/m^2 IV and Cytarabine 1 g/m^2 IV for two days, + Rituximab 375 mg/m^2 IV on Day 3, Cycle 1 then Day 1 following cycles.
干预措施: Cytarabine (Drug)
Oxaliplatin, Fludarabine, Cytarabine + Rituximab
Starting dose oxaliplatin 17.5mg/m^2/day intravenous (IV) for 4 days; Fludarabine 30 mg/m^2 IV and Cytarabine 1 g/m^2 IV for two days, + Rituximab 375 mg/m^2 IV on Day 3, Cycle 1 then Day 1 following cycles.
干预措施: Fludarabine (Drug)
Oxaliplatin, Fludarabine, Cytarabine + Rituximab
Starting dose oxaliplatin 17.5mg/m^2/day intravenous (IV) for 4 days; Fludarabine 30 mg/m^2 IV and Cytarabine 1 g/m^2 IV for two days, + Rituximab 375 mg/m^2 IV on Day 3, Cycle 1 then Day 1 following cycles.
干预措施: Oxaliplatin (Drug)
Oxaliplatin, Fludarabine, Cytarabine + Rituximab
Starting dose oxaliplatin 17.5mg/m^2/day intravenous (IV) for 4 days; Fludarabine 30 mg/m^2 IV and Cytarabine 1 g/m^2 IV for two days, + Rituximab 375 mg/m^2 IV on Day 3, Cycle 1 then Day 1 following cycles.
干预措施: Rituximab (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) Oxaliplatin
时间窗: From treatment onset to end of each cycle of treatment (every 21 days)
MTD defined as dose level at which 2/3 or 2/6 participants experience Dose Limiting Toxicity (DLT), where DLTs are any oxaliplatin-related ≥Grade 3 non-hematological toxicity involving a major organ system (brain, heart, kidney, liver, lung) in the National Cancer Institute (NCI) Version 3.0 toxicity scale.
次要结局
- Number of Participants With a Complete Response or Partial Response(Evaluation every 3 cycles of treatment (28 days per cycle), approximately 90 days)