This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This phase I study tests the safety of a new experimental drug called PS-341 (Velcade or Bortezomib) in refractory/recurrent leukemia patients. (Leukemia is a type of cancer that affects a child's blood cells, recurrent means the disease came back after being treated, and refractory means that the disease is hard to treat.) Laboratory experiments performed with PS-341 showed that it kills cancer cells by stopping their growth. A safe dose of PS-341 has already been found in adults and in children with solid tumors, but a safe dose has not been found in children with leukemia. The goals of this study are to test the safety of PS-341, to see what effects (good and bad) they have on children and children's leukemia, and to find the highest dose of PS-341 that can be given to children with leukemia without causing severe side effects. Other goals of this study are to learn how the body handles the drug, and to better understand how cancer cells are different from healthy cells. The study is designed such that the children are separated into groups. The first group of children will be given PS-341 at the starting dose. If the side effects at the starting dose are not too serious, the next group of children will be given a higher dose of PS-341. This will continue until the maximum dose is found that does not result in unacceptable side effects. The dose of PS-341 given will not be increased in each individual child. Each course of therapy will last 21 days. During each course, the patient will be given PS-341 on days 1, 4, 8 and 11 of each course. PS-341 will be given through a vein. A sample overview of a treatment course is below: Monday Tuesday Wednesday Thursday Friday Saturday Sunday Week 1 PS-341 PS-341 Week 2 PS-341 PS-341 Week 3 Rest period; no PS-341 is given this week Day 18-22 Evaluation: retreat if disease is not worse and side effects are tolerable Children on this study will be given standard medical exams during therapy, such as physical exams, protein level tests and tests to examine liver and kidney function. A bone marrow aspirate will be done at the end of every course for the first three courses, and then at the end of every other course. In addition to these standard tests, patients will be the given the option to have blood samples taken on a few days during the first course of therapy for tests called pharmacokinetics. Pharmacokinetic tests find out how the drug is behaving in cells in the body. Patients will also be given the option to participate in other special research studies involving their bone marrow and blood samples.
Showing the most recent 10 out of 563 publications
