Phase II Randomized Study Evaluating the Addition of Rituximab to the Preparative Regimen of Etoposide and Total Body Irradiation in Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Progression-free Survival (PFS)
研究概览
简要总结
Primary Objective:
- To determine the progression free survival (PFS) of the preparative regimen rituximab, etoposide and total body irradiation (TBI), in patients with acute lymphoblastic leukemia (ALL) receiving allogeneic hematopoietic stem cell transplantation (SCT).
Secondary Objectives:
- To determine the effect of rituximab on the incidence of acute graft vs. host disease (GVHD).
- To determine the efficacy of adding imatinib mesylate post transplant in ALL patients with the t(9;22)(q34;q11) cytogenetic abnormality.
- To estimate the probability of molecular complete remission at one year for the described treatment approach as determined by serial minimal residual disease (MRD) monitoring.
- To determine the rate of GVHD, engraftment, toxicity, and overall survival (OS) for this treatment regimen.
详细描述
Disease relapse and GVHD are 2 factors that significantly impact survival in ALL patients who receive SCT. GVHD occurs when donor cells (graft) attack the stem cell recipient's (host's) cells. The term "acute" refers to the time it takes for the GVHD to appear after the transplant. This time frame is usually within the first 100 days after the transplant. GVHD occurs in up to 50% of patients who receive a transplant.
Etoposide is a traditional chemotherapy drug that is designed to interfere with the production of cancer cells at the DNA and RNA level. Total body irradiation (TBI) uses low level radiation to also interfere with the production of cancer cells at the DNA and RNA level. The combination of etoposide and TBI is a standard transplant conditioning therapy used for ALL patients. Rituximab is a monoclonal antibody that is designed to work against cells that express the antigen CD20. In addition, some studies suggest that it may decrease the risk of GVHD.
Before you can start treatment on this study, you will have what are called "screening tests". These tests will help the doctor decide if you are eligible to take part in the study. You will have a complete medical history and physical exam, including routine blood (2-3 teaspoons) and urine tests. You will have a chest x-ray, heart scan (echocardiogram or MUGA scan (Multi Gated Acquisition Scan)), lung function test, and a bone marrow biopsy with aspirate to evaluate the status of your disease before transplant. To collect a bone marrow biopsy and aspirate, an area of the hip or chest bone is numbed with anesthetic, and a small amount of bone marrow and bone is withdrawn through a large needle. A bone marrow core (a solid piece from the bone marrow) is also collected through a hollow needle inserted into the hip bone. Women who are able to have children must have a negative blood pregnancy test.
If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to one of 2 treatment groups. Participants in one group will receive etoposide and TBI before their transplant. Participants in the other group will receive etoposide, TBI, and rituximab before their transplant. There is an equal chance of being assigned to either group. You will receive treatment on this study as an inpatient.
On the 1st day of hospitalization, you will receive fluids by vein through a central venous catheter (a plastic tube inserted into a large vein under your collar bone). You will receive TBI, once a day for the next 4 days. During TBI, you will lie flat on a table and receive radiation beams to all parts of the body, with shielding over certain parts of the body. On the following day, you will receive etoposide through the catheter over 4 hours. You will then have 2 days of rest, followed by your transplant of stem cells. The stem cells will be infused into your vein. The infusion can last from 30 minutes to several hours.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with biopsy-proven ALL in remission or relapse.
- •Adequate renal function, as defined by estimated serum creatinine clearance >50 ml/min and/or serum creatinine <1.8 mg/dL.
- •Adequate hepatic function, as defined by aspartate aminotransferase (AST) or serum glutamic oxaloacetic transaminase (SGOT) <3 * upper limit of normal; serum bilirubin and alkaline phosphatase <2 * upper limit of normal, or considered not clinically significant.
- •Adequate pulmonary function with Forced Expiratory Volume in One Second (FEV1), forced vital capacity (FVC) and Carbon Monoxide Diffusing Capacity (DLCO) at least 45% of expected corrected for hemoglobin.
- •Adequate cardiac function with left ventricular ejection fraction at least 45%. No uncontrolled arrhythmias or symptomatic cardiac disease.
- •Zubrod performance status <
- •Patients must have a related, genotypically human leukocyte antigens (HLA) identical donor, or they must have a related or unrelated donor who is at least a 9/10 HLA match by high resolution typing.
- •Female patient must not be pregnant and have negative pregnancy test.
- •Patient and donor should be willing to participate in the study by providing written consent.
排除标准
- •Patients with unresolved grade 3 or greater non-hematologic toxicity from previous therapy. Patients with grade 2 toxicity will be eligible at the discretion of the principal investigator (PI).
- •Patients with active central nervous system (CNS) disease.
- •Evidence of acute or chronic active hepatitis or cirrhosis.
- •Uncontrolled infection, including Human immunodeficiency virus (HIV) or Human T-lymphotropic virus Type I (HTLV-1) infection.
- •Patients greater than 60 years-old.
- •Prior autologous or allogeneic hematopoietic stem cell transplant.
研究组 & 干预措施
Etoposide + Total Body Irradiation + Rituximab
Etoposide 60 mg/kg intravenous (IV) Daily Over 4 Hours for 1 Day + Total Body Irradiation (TBI) 3 Gy Daily for 4 Days + Rituximab 375 mg/m^2 IV Weekly Over 4-8 Hours for 4 Weeks
干预措施: Etoposide (Drug)
Etoposide + Total Body Irradiation + Rituximab
Etoposide 60 mg/kg intravenous (IV) Daily Over 4 Hours for 1 Day + Total Body Irradiation (TBI) 3 Gy Daily for 4 Days + Rituximab 375 mg/m^2 IV Weekly Over 4-8 Hours for 4 Weeks
干预措施: Total Body Irradiation (Radiation)
Etoposide + Total Body Irradiation + Rituximab
Etoposide 60 mg/kg intravenous (IV) Daily Over 4 Hours for 1 Day + Total Body Irradiation (TBI) 3 Gy Daily for 4 Days + Rituximab 375 mg/m^2 IV Weekly Over 4-8 Hours for 4 Weeks
干预措施: Rituximab (Drug)
Etoposide + Total Body Irradiation
Etoposide 60 mg/kg IV Daily Over 4 Hours for 1 Day + TBI 3 Gy Daily for 4 Days
干预措施: Etoposide (Drug)
Etoposide + Total Body Irradiation
Etoposide 60 mg/kg IV Daily Over 4 Hours for 1 Day + TBI 3 Gy Daily for 4 Days
干预措施: Total Body Irradiation (Radiation)
结局指标
主要结局
Progression-free Survival (PFS)
时间窗: 2 Years post transplant or until disease progression or death
Time from randomization to first progression or death, whichever comes first, measured in months.
次要结局
- Number of Participants With Incidence of Acute Graft Versus Host Disease During First 100 Days(During the first 100 days following transplant)