Pharmacokinetic Evaluation of Rasburicase Dosed for 5 Consecutive Days as Uricolytic Therapy in Adult Patients With Leukemia and/or Lymphoma at High or Potential Risk of Tumor Lysis Syndrome (TLS)
18 Years
N/A
Both
Leukemia, Lymphoma, Tumor Lysis Syndrome
Trial Information
Pharmacokinetic Evaluation of Rasburicase Dosed for 5 Consecutive Days as Uricolytic Therapy in Adult Patients With Leukemia and/or Lymphoma at High or Potential Risk of Tumor Lysis Syndrome (TLS)
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.
Inclusion Criteria:
1. Age >/= 18
2. Risk of TLS: A. High risk: hyperuricemia of malignancy; diagnosis of aggressive
lymphoma/leukemia based on Revised European-American Lymphoma (REAL) classification;
acute myeloid leukemia in blast crisis; high grade myelodysplastic syndrome only if
they have >10% bone marrow blast involvement and given aggressive treatment similar
to AML; OR B. Potential risk: diagnosis of aggressive lymphoma/leukemia based on
(REAL) classification. Plus one or more of the following criteria: LDH >/=2 x ULN;
Stage III-IV disease; Stage I-II disease with at least 1 lymph node/tumor >5cm in
diameter.
3. ECOG performance status 0-3
4. Life expectancy >3 months
5. Negative pregnancy test (females of child bearing potential) within rasburicase dose and use of efficient contraceptive method (both males and females).
Pregnancy test may be performed on serum (HCG) or urine (HCG)
6. Signed written informed consent (approved by the Institutional Review Board/Ethics
Committee) obtained prior to study entry
Exclusion Criteria:
1. Patient receiving any investigational drug for hyperuricemia within 30 days of
planned first treatment with rasburicase
2. Pregnancy or lactation
3. Known history of significant allergy problem or documented history of asthma or
asthmatic bronchitis
4. Known history of glucose-6-phosphate dehydrogenase deficiency
5. Known history of hemolysis and methemoglobinemia
6. Positive tests for HBs antigen, HCV antibodies, or HIV-1, 2 antibodies
7. Hypersensitivity to uricases or any of the excipients
8. Previous therapy with urate oxidase
9. Other conditions unsuitable for participation in the trial in the Investigator's
opinion
10. Unwilling to comply with the requirements of the protocol
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Effectiveness of rasburicase in treatment of patients with leukemia and/or lymphoma who are at high or potential risk for TLS.
Outcome Time Frame:
4 Years
Safety Issue:
Yes
Principal Investigator
Saroj Vadhan-Raj, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Food and Drug Administration
Study ID:
2006-0298
NCT ID:
NCT00360438
Start Date:
July 2006
Completion Date:
April 2007
Related Keywords:
- Leukemia
- Lymphoma
- Tumor Lysis Syndrome
- Leukemia
- Lymphoma
- Tumor Lysis Syndrome
- TLS
- Rasburicase
- Elitek
- Leukemia
- Lymphoma
- Tumor Lysis Syndrome
Name | Location |
|---|---|
| The University of Texas M.D. Anderson Cancer Center | Houston, Texas |
