A Phase II Study of High-Dose Intravenous Busulfan Plus Melphalan With Allogeneic or Autologous Marrow or Peripheral Blood Progenitor Cell Transplantation for Lymphoid Malignancies or Multiple Myeloma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 168
- 试验地点
- 1
- 主要终点
- Average Overall Survival Time
研究概览
简要总结
Primary Objectives:
- To determine the efficacy of administering multiple doses of intravenous (i.v.) busulfan at a dose of 130 mg/m2, to yield a systemic plasma drug exposure represented by a daily area under the plasma concentration versus time curve (AUC) of approximately 5,000 mMol-min for 4 days, followed by i.v. melphalan at a dose of 70 mg/m2 for 2 days in adult patients receiving autologous or allogeneic transplantation for lymphoid malignancies or myeloma.
- To describe the plasma pharmacokinetic (PK) profiles of busulfan and melphalan in this regimen.
- To determine the disease-free and overall survival of patients receiving this preparative regimen.
- To determine the treatment-related morbidity and mortality of this combination of drugs.
详细描述
Busulfan and melphalan are both traditional alkylating agents that are designed to interfere with the production of cancer cells at the DNA (deoxyribonucleic acid) and RNA (ribonucleic acid) level.
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 physical exam, including routine blood (2-3 teaspoons) and urine tests. Patients will have a chest x-ray, heart scan, lung function test, and a bone marrow biopsy. 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 able to start receiving chemotherapy treatment with busulfan and melphalan. Participants who agree to the optional blood draws described above will at first receive a therapeutic "trial dose" of busulfan by vein to test the blood levels over time. This therapeutic trial dose of busulfan is about 25% (1 fourth) of the full therapeutic dose of the drug. This information will be used to decide what the future high-dose busulfan treatments you receive will be. If you do not agree to the optional blood draw, you will receive a fixed amount of high-dose busulfan from the start.
On the 1st day of hospitalization, you will receive fluids by vein through a central venous catheter. If you choose the optional busulfan dose for pharmacokinetic-based busulfan dosing, you will receive the optional busulfan dose 9 days before stem cell infusion (Day 1), followed by a rest day on Day 2. If you choose to receive a fixed dose of busulfan, busulfan will be injected through a central venous catheter over 3 hours, once a day, for the next 4 days (Days 3-6, ending 3 days before the stem cell infusion day).
Patients receiving pharmacokinetic-based dosing of busulfan will also continue to receive busulfan on Days 3-6. This will be followed by melphalan for all patients, given through your central venous catheter over 30 minutes, once a day, for 2 days, on days 8 and 9. Your stem cell infusion day will be on Day 10 of treatment.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with lymphoid malignancies, including Hodgkin's and non-Hodgkin's lymphoma (primary refractory or recurrent), or multiple myeloma (beyond first complete remission or unresponsive to therapy. Complete remission for multiple myeloma defined by absence of detectable paraprotein in serum and/or urine by immunoelectrophoresis or immunofixation, and < 5% plasma cells in the bone marrow), not qualifying for treatment protocols of higher priority.
- •Age 18 to 65 years of age.
- •Adequate renal function as defined by estimated serum creatinine clearance > 50 ml/min and serum creatinine < 1.8 mg/dL.
- •Adequate hepatic function, as defined by serum glutamic pyruvic transaminase (SGPT) < 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 Capacity of the Lung for Carbon Monoxide (DLCO)> 50%. Exceptions may be allowed for patients with pulmonary involvement after discussing with principal investigator (PI).
- •Adequate cardiac function with left ventricular ejection fraction >/= 40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
- •Zubrod performance score <
- •Patients receiving an allogeneic transplant must have an HLA matched, or one A, B, or DR mismatched related donor. Unrelated donor must be matched at A, B, and DR (defined as A, B serologic matched and DRB1 molecular matched). Donor must be willing to donate peripheral blood or bone marrow progenitor cells.
- •Patient and donor should be willing to participate in the study by providing written consent.
- •Female patient must not be pregnant and have negative pregnancy.
排除标准
- •Patients with unresolved grade >/= 3 non-hematologic toxicity from previous therapy. Patients with grade 2 toxicity will be eligible at the discretion of the PI.
- •Patients with active Central Nervous System (CNS) disease.
- •Evidence of acute or chronic active hepatitis or cirrhosis. If positive hepatitis serology, discuss with Study Chairman and consider liver biopsy.
- •Uncontrolled infection, including Human immunodeficiency virus (HIV) or Human T-lymphotropic virus Type I (HTLV-1) infection.
- •Patients who have had a previous autologous or allogeneic stem cell transplant during the past year.
研究组 & 干预措施
Busulfan + Melphalan
Busulfan 32 mg/m^2 intravenous (IV) for 1 Day then 130 mg/m^2 IV for 4 Days; and Melphalan 70 mg/m^2 IV for 2 Days
干预措施: Busulfan (Drug)
Busulfan + Melphalan
Busulfan 32 mg/m^2 intravenous (IV) for 1 Day then 130 mg/m^2 IV for 4 Days; and Melphalan 70 mg/m^2 IV for 2 Days
干预措施: Melphalan (Drug)
结局指标
主要结局
Average Overall Survival Time
时间窗: Baseline(transplantation) to disease progression or death for any reason, up to 6 years.
Average number of years for survival post transplant where overall survival time is measured from date of transplant to disease progression or death for any reason.
次要结局
未报告次要终点