Randomized, Double-Blind, Placebo Controlled Trial of Voraxaze™ in Patients With a Delayed MTX Clearance
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 1
- 主要终点
- Patient Response Rate (Percentage)
研究概览
简要总结
Primary Objectives:
- To evaluate the efficacy of Glucarpidase (Voraxaze) in increasing the rate of methotrexate (MTX) clearance following high dose MTX treatment in patients with a delayed MTX clearance.
- To evaluate the pharmacokinetics (PK) of Glucarpidase following high dose MTX treatment in patients with a delayed MTX clearance.
- To evaluate the safety profile of Glucarpidase following high dose MTX treatment in patients with a delayed MTX clearance.
Secondary Objectives:
- To evaluate the effect of Glucarpidase on the incidence of neutropenic fever and use of intravenous (IV) antibiotics.
- To evaluate the effect of Glucarpidase on the length of hospitalization.
- To evaluate the effect of Glucarpidase on renal function.
- To evaluate the effect of Glucarpidase on Quality of Life (QOL).
- To evaluate the anti-glucarpidase antibody response.
- To evaluate the efficacy of Glucarpidase following its use in repeated cycles of high dose MTX treatment.
详细描述
Researchers want to learn how glucarpidase may impact patients' length of stay in the hospital, kidney function, and quality of life. Also, researchers want to learn if glucarpidase may decrease the incidence of neutropenic fever, which may decrease the use of antibiotics by vein to treat this kind of fever.
MTX is a high-dose chemotherapy drug that reduces the supply of an important vitamin (folate) required for the growth of cancer cells. In patients with delayed clearance of MTX from the body, there is a risk of more frequent or severe side effects from the drug.
Glucarpidase is a drug that breaks down MTX in the blood, causing the drug to be less toxic and decreasing levels of the drug in the blood.
Before you can start treatment on this study, you will have "screening tests." These tests will help the doctor decide if you are eligible to take part in this study. Your complete medical history will be recorded. You will have a physical exam, including measurement of your vital signs (temperature, pulse, breathing rate, and blood pressure). You will have blood drawn (about 3 teaspoons) for routine tests. You will also have blood drawn (about 1 teaspoon), right before treatment starts, 28 days after the first dose of study drug in each cycle, and at the end of the study to see if you have any antibodies (proteins in the body that help fight infections and foreign substances in the body) to the study drug. Women who are able to have children must have a negative blood pregnancy test. The blood used for the pregnancy test will come from the sample taken for routine tests. (There is no additional blood draw for the pregnancy test).
You may be given either glucarpidase or placebo (a drug that looks like glucarpidase but is not active). Neither you nor the study doctor will know if you have been given glucarpidase or placebo. This is called the blinded phase of this study. Before you can begin on this study, if you are already suffering from side effects (because of difficulty with MTX clearance), such as kidney toxicity, severe mucositis (redness and painful ulcers in the mouth), and/or you have extremely high MTX levels, you will not be randomized and will receive glucarpidase, not placebo. If this is the case, your doctor will know that you have been given glucarpidase.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- Double (Participant, Investigator)
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with solid tumors and hematologic malignancies, receiving high dose methotrexate (MTX) (> / = 1 g/m^2 up to 14 g/m^2), who have delayed MTX clearance. Delayed MTX clearance is defined as: a) Serum MTX level at 72 +/- 2 hrs from initiation of infusion > / = 0.1 µmol/L for MTX doses 1-3.5 g/m^2 OR b) Serum MTX level at 72 +/- 2 hrs from initiation of infusion > / = 0.3 µmol/L for MTX doses > 3.5 g/m^2
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- •IRB-approved signed informed consent
排除标准
- •Any medical or psychiatric illness that is deemed by the investigator to be likely to interfere with patient's ability to sign informed consent, cooperate and participate in the study
- •Patients receiving medications which may interfere with MTX excretion or enhance MTX toxicity (e.g. Penicillins, Cephalosporins, Tetracyclines, Non-Steroidal Anti-inflammatory Agents, Salicylates, Thiazide Diuretics, Bactrim, and Probenecid)
- •Patients with uncontrolled cardiac disease such as uncontrolled angina, cardiac arrhythmia, or Congestive Heart Failure (CHF) (New York Heart Association (NYHA) 4)
- •Patients with known hypersensitivity to any of the components of the study drug
研究组 & 干预措施
Voraxaze
Voraxaze administered 50 units/kg intravenously (IV) repeated a maximum of 2 times in a given cycle of chemotherapy.
干预措施: Voraxaze (Glucarpidase) (Drug)
Placebo
Placebo administered IV following Voraxaze arm.
干预措施: Placebo (Drug)
结局指标
主要结局
Patient Response Rate (Percentage)
时间窗: Study period 2 years
Response rate defined as proportion of patients that clear methotrexate (MTX) at 15 min and 24-hour post infusion of study drug, Glucarpidase (Voraxaze) to total patient number. Serum MTX levels (standard methods and mass spectrometry) at 15 minutes, 24 hours, or daily until MTX clearance defined as serum MTX level \<0.1 µmol/L.
次要结局
未报告次要终点