Pharmacokinetic Evaluation of Rasburicase in Patients With Leukemia and/or Lymphoma at High Risk of TLS
Summary
Primary
1. To determine the pharmacokinetic (PK) parameters of rasburicase in adult patients with leukemia and/or lymphoma at high risk or potential risk of tumor lysis syndrome (TLS)
Secondary
1. To evaluate plasma uric acid AUC from baseline (within 4 hours prior to first rasburicase treatment) through 48 hours after the last per-protocol planned administration of rasburicase treatment;
2. To evaluate the safety of rasburicase in adult patients with leukemia and/or lymphoma.
3. To evaluate incidence, duration, and type of immune responses (IgG, IgE, and neutralizing antibody) to rasburicase.
Description
Rasburicase is designed to help decrease or prevent the high level of uric acid that may occur during the start of chemotherapy. A high level of uric acid may lead to reduced kidney function or kidney failure.
TLS occurs when high uric acid levels are caused by breakdown of tumor cells after the start of chemotherapy. The dead tumor cells can release uric acid and other symptoms of kidney failure, such as excessive amounts of potassium and phosphorus, into 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, and you will have a physical exam, including measurement of your vital signs (blood pressure, heart rate, temperature, and breathing rate), height, and weight. You will have blood drawn (about 2 tablespoons) for routine tests. Women who are able to have children must have a negative blood (a sample will be used from the routine blood draw) or urine pregnancy test.
If you are found to be eligible to take part in this study, you will receive rasburicase by a needle in your vein over 30 minutes once a day for 5 days in a row. You will receive chemotherapy within 4-24 hours after your first dose of rasburicase.
On Days 1-5 (study drug treatment period), you will have a physical exam, including measurement of your vital signs. During this time, you will have blood drawn (about 2 tablespoons each) once a day for routine tests.
You will have blood drawn (less than 1 teaspoon each) for PK testing at different time points throughout this study. PK tests measure the level of the study drug in the blood at different times. You will have a total of 14 samples drawn. Your blood will be drawn on Day 1 before your dose of rasburicase and then at 30 minutes and at 4, 8, 24, 48, 72, 96, 96.5,100,104,120 (Day 6),168 (Day 8), and 336 (Day 15) hours after your dose of the study drug.
You will have blood drawn (less than 1 teaspoon each) to measure the level of uric acid in your blood at different time points throughout this study so that researchers can learn the effectiveness of the study drug on your disease. You will have a total of 7 samples drawn. Your blood will be drawn on Day 1 before your dose of rasburicase and then at 4, 24, 48, 72, 96,120 (Day 6), and 144 (Day 7) hours after your dose of the study drug.
You will also have blood drawn (less than 1 teaspoon each) for antibody testing at different time points throughout this study. Antibody testing is a method to check for proteins (IgG) made by your body that show that your body is reacting to rasburicase. You will have at least 5 samples drawn. Your blood will be drawn on Day 1 before your dose of rasburicase and then on Day 14, Day 35, and at 3 and 6 months after your dose of the study drug.
If you have a positive IgG (antibody protein) at the 6-month blood draw for antibody testing, you will continue to have blood drawn (less than 1 teaspoon) every 6 months until your antibody protein is negative.
If you experience any side effects related to allergic reactions during treatment with the study drug (up to 30 days after your last dose of the study drug), you will have an additional blood draw (less than 1 teaspoon) for antibody testing within 48 hours after having the reaction.
You will be taken off this study if your disease gets worse or you experience any intolerable side effects.
You will have assessments after the end of your study drug treatment (from Days 1 to 5). These assessments will include a physical exam, including measurement of your vital signs, on Days 14 and 35. You will also have blood drawn (about 2 tablespoons each) for routine tests on Days 8 and 14.
This is an investigational study. Rasburicase is authorized by the FDA for use (in adults) in research only. Rasburicase will be provided free of charge during this study. Up to 20 patients will take part in this multicenter study. Up to 20 can be enrolled at M. D. Anderson.
Study Design
Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Leukemia
Intervention
Rasburicase
Location
The University of Texas M.D. Anderson Cancer Center
Houston
Texas
United States
77030
Status
Completed
Source
M.D. Anderson Cancer Center
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00360438
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Abelson Murine Leukemia Virus
A replication-defective strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) capable of transforming lymphoid cells and producing a rapidly progressing lymphoid leukemia after superinfection with FRIEND MURINE LEUKEMIA VIRUS; MOLONEY MURINE LEUKEMIA VIRUS; or RAUSCHER VIRUS.
Friend Murine Leukemia Virus
A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) producing leukemia of the reticulum-cell type with massive infiltration of liver, spleen, and bone marrow. It infects DBA/2 and Swiss mice.
Moloney Murine Leukemia Virus
A strain of Murine leukemia virus (LEUKEMIA VIRUS, MURINE) arising during the propagation of S37 mouse sarcoma, and causing lymphoid leukemia in mice. It also infects rats and newborn hamsters. It is apparently transmitted to embryos in utero and to newborns through mother's milk.
Leukemia, Prolymphocytic
A chronic leukemia characterized by a large number of circulating prolymphocytes. It can arise spontaneously or as a consequence of transformation of CHRONIC LYMPHOCYTIC LEUKEMIA.
Leukemia, Prolymphocytic, T-cell
A lymphoid leukemia characterized by a profound LYMPHOCYTOSIS with or without LYMPHADENOPATHY, hepatosplenomegaly, frequently rapid progression, and short survival. It was formerly called T-cell chronic lymphocytic leukemia.
Clinical Trials
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Elitek (Rasburicase) Immuno-Monitoring Study
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PubMed Articles
Economic Implications of Rasburicase Treatment in Adult Patients with Tumour Lysis Syndrome.
Background: Rasburicase is a recombinant urate-oxidase enzyme used to reduce high levels of plasma uric acid (PUA) resulting from tumour lysis syndrome (TLS). Rasburicase reduces PUA levels within 4 h...
BACKGROUND: Rasburicase is indicated for the initial management of plasma uric acid levels in adults receiving anticancer therapy who are at risk for acute tumor lysis syndrome (TLS) and subsequent hy...
PURPOSE Rasburicase is effective in controlling plasma uric acid in pediatric patients with hematologic malignancies. This study in adults evaluated safety of and compared efficacy of rasburicase alon...
Refrigeration is not necessary for measurement of uric acid in patients treated with rasburicase.
Abstract Background: Rasburicase, used for hyperuricemia of tumor lysis syndrome, retains activity at room temperature (RT) in in vitro studies. Cold-temperature handling is recommended for uric acid...
ABSTRACT: INTRODUCTION: Transient myeloproliferative disorder is a hematologic abnormality characterized by an uncontrolled proliferation of myeloblasts in peripheral blood and bone marrow that primar...
