Dose Escalation Trial of Cloretazine (VNP40101M) and Hematopoietic Cell Transplantation for Patients With Selected, Poor-Prognosis Hematologic Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 5
- 试验地点
- 1
- 主要终点
- To study the highest tolerable dose of VNP40101M that can be given to patients with a form of leukemia, MDS, lymphoma, or myeloma in preparation for an autologous stem cell transplant.
研究概览
简要总结
Primary:
Define the maximal tolerated dose (MTD) of VNP40401M when given with hematopoietic cell transplantation (HCT)
Secondary:
- Describe the change in pharmacokinetic (PK) parameters with increasing doses of drug.
- Describe and estimate the frequency of > Grade 3 non-hematologic/non-infectious toxicities at the MTD.
- Report the efficacy of the regimen.
- Evaluate the rate of engraftment for the regimen.
详细描述
An autologous transplant uses the recipient's own stem cells, from the blood and bone marrow, for infusion.
VNP40101M is a chemotherapy drug designed to interfere with the growth and development of cancer cells, by binding to structures within cancer cells. This drug, given in higher doses, causes lowering of blood cells. Chemotherapy is commonly given to patients before a stem cell transplantation to help kill more cancer cells. After receiving this drug, stem cells are transfused (given gradually) to allow re-growth of the blood cells.
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 this study. You will have blood drawn (about 3 tablespoons) for routine tests. You will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate). You will have a bone marrow biopsy. To collect a bone marrow biopsy, an area of the hip or chest bone is numbed with anesthetic, and a small amount of marrow and bone is withdrawn through a large needle. You will have a chest x-ray and computed tomography (CT) and positron emission tomography (PET) scans, if required, to measure your tumor. You will have a lung function test and an electrocardiogram (ECG-a test to measure the electrical activity of the heart). Women who are able to have children must have a negative blood or urine pregnancy test. If you will have a blood pregnancy test it will be done with routine blood tests.
Before you receive treatment on this study, you will have apheresis done to collect some of your stem cells. Apheresis is the process of removing part of the blood (such as platelets or white blood cells) from the body in order to remove certain elements, such as stem cells. Then the rest of the blood is returned back to the body. Your stem cells will be put back in your body after you finish treatment with VNP40101M. Apheresis will be done by a major vein through a central venous catheter (CVC), usually in the chest. A CVC is a sterile flexible tube that will be placed into a large vein while you are under local anesthesia. The details of apheresis as well as the CVC will be described in separate consent forms. Your doctor will explain these procedures to you in more detail, and you will be required to sign a separate consent form for each procedure.
If you are found to be eligible to take part in this study, you will receive a dose of VNP40101M. The dose you receive will depend on when you enrolled in this study. The dose that you receive will remain the same throughout this study. Researchers will continue to enroll patients at the next highest dose level until the highest tolerable dose is found.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 to 65 years for autotransplant patients and age 18 to 60 years for allotransplant patients.
- •Patients with acute leukemia/MDS or lymphoid malignancies, including Hodgkin's and non-Hodgkin's lymphoma (primary refractory or refractory relapse), or multiple myeloma (beyond first remission or unresponsive to therapy), not qualifying for treatment protocols of higher priority.
- •Adequate renal function, as defined by serum creatinine <1.5 mg/dL.
- •Adequate hepatic function, as defined by SGPT <3 X upper limit of normal; serum bilirubin and alkaline phosphatase <2 X upper limit of normal, or considered not attributable to liver disease in the case of alkaline phosphatase.
- •Adequate pulmonary function with FEV1, FVC and DLCO >50% of expected corrected for hemoglobin.
- •Adequate cardiac function with left ventricular ejection fraction >40%. No uncontrolled arrhythmias or symptomatic cardiac disease.
- •Zubrod performance status <2
- •Patients receiving an allogeneic transplant must have a related or unrelated donor which meets departmental standards for donor selection.
排除标准
- •Uncontrolled life-threatening infections
- •HIV positive
- •A positive Beta HCG in a woman with child bearing potential as defined as not being post-menopausal for 12 or more months or no previous surgical sterilization procedures.
- •Any CNS involvement which has not been controlled for at least 4 weeks
- •Patients must be at least 21 days from prior systemic therapy for their malignancy, or have improvement of all reversible toxicities to </= grade 2, whichever occurs first.
- •Any patient receiving Antabuse
- •Patients should be off metronidazole (Flagyl) for at least 24 hours prior to starting VNP40401M
研究组 & 干预措施
Cloretazine + Fludarabine
干预措施: Cloretazine (Drug)
Cloretazine + Fludarabine
干预措施: Fludarabine (Drug)
结局指标
主要结局
To study the highest tolerable dose of VNP40101M that can be given to patients with a form of leukemia, MDS, lymphoma, or myeloma in preparation for an autologous stem cell transplant.
时间窗: 2 Years
次要结局
未报告次要终点