Rasburicase in Patients at Risk for Tumor Lysis Syndrome

Tracking Information
First Submitted Date ICMJE	February 25, 2008
First Posted Date ICMJE	March 5, 2008
Results First Submitted Date	May 31, 2013
Results First Posted Date	August 1, 2013
Last Update Posted Date	August 1, 2013
Study Start Date ICMJE	January 2008
Actual Primary Completion Date	May 2012 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: May 31, 2013)	Number of Participants With Plasma Uric Acid (UA) Response [ Time Frame: First cycle of chemotherapy, up to 5 days ]; Plasma UA response is defined as normalization of plasma UA levels within 48 hours after the start of study drug (rasburicase) and maintaining within the normal range after the final drug infusion on day 5. Plasma samples for UA were collected at baseline before rasburicase, 4- and 24-hours post-rasburicase, and daily during treatment.
Original Primary Outcome Measures ICMJE; (submitted: February 25, 2008)	The goal of this clinical research study is to compare how well rasburicase given in 2 different ways can help control or prevent TLS in patients who are at risk for TLS. [ Time Frame: 17 Months ]
Change History	Complete list of historical versions of study NCT00628628 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE	Not Provided
Original Secondary Outcome Measures ICMJE; (submitted: February 25, 2008)	The safety of this treatment will also be studied. [ Time Frame: 17 Months ]
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Rasburicase in Patients at Risk for Tumor Lysis Syndrome
Official Title ICMJE	Phase 2 Study of Rasburicase Administered by Two Different Schedules (Fixed Dosing vs. As Needed Dosing) in Patients at High Risk or Potential Risk for Tumor Lysis Syndrome
Brief Summary	Primary Objectives: To determine the efficacy of rasburicase administered as a single dose followed by as needed dosing (investigational arm) as compared to fixed dosing for 5 days (standard treatment arm) in the treatment of patients at high risk or potential risk for tumor lysis syndrome. Secondary Objectives: To evaluate the plasma uric acid area under the curve (AUC) from baseline through 7 days; To evaluate the incidence of renal insufficiency and electrolyte abnormalities.; To determine the safety and immunogenicity of rasburicase.; To evaluate the cost-effectiveness of the experimental treatment (investigational arm).
Detailed Description	The Study Drug and 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 in the blood may lead to decreased kidney function or kidney failure. TLS occurs when high uric acid levels are caused by breakdown of tumor cells during the start of chemotherapy. The dead tumor cells can release uric acid and cause other symptoms of kidney failure, such as releasing large amounts of potassium and phosphorus (chemicals) into the blood. Screening Tests 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 (blood pressure, heart rate, temperature, and breathing rate), height, and weight. Blood will be drawn (about 2 tablespoons) for routine tests. Women who are able to have children must have a negative blood (using a sample from the routine blood draw) or urine pregnancy test. Study Groups If you are found to be eligible to take part in this study, you will be randomly assigned (as in the toss of a coin) to 1 of 2 groups. There is an equal chance of being in either group. Group A Participants in Group A will receive rasburicase by vein, over 30 minutes, on Day 1 of Cycle 1 of chemotherapy. On Days 1-7 of Cycle 1 of chemotherapy, blood (about 2 tablespoons) will be drawn for routine tests, including a check of the level of uric acid in your blood. During Days 2-5 of Cycle 1 of chemotherapy, you will only receive rasburicase (once a day) if the levels of uric acid are high that day. Group B Participants in Group B will receive rasburicase by vein, over 30 minutes, once a day from Days 1-5 of Cycle 1 of chemotherapy. On Days 1-7 of Cycle 1 of chemotherapy, blood (about 2 tablespoons) will be drawn for routine tests, including a check of the level of uric acid in your blood. Both Groups Treatment with rasburicase will only be given in Cycle 1 of chemotherapy. The chemotherapy will be given at least 4 hours (up to 24 hours) after the first dose of rasburicase. Length of Study When your blood test results show that you do not have antibodies to rasburicase, your participation in this study will be over. You will be taken off this study if the TLS gets worse or intolerable side effects occur. This is an investigational study. Rasburicase is commercially available, but it is not FDA approved for treating TLS. It is FDA approved for pediatric patients with leukemia, lymphoma, and solid tumor cancers who are receiving anti-cancer therapy that is expected to increase the blood levels of uric acid (the result of cancer cells dying from treatment). For treating TLS in adult patients, it has been authorized for use in research only. Up to 80 evaluable patients will take part in this study. All will be enrolled at M. D. Anderson.
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Tumor Lysis Syndrome
Intervention ICMJE	Drug: As Needed Rasburicase .15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed. Other Name: Elitek™; Drug: Fixed Dose Rasburicase .15 mg/kg IV Over 30 Minutes Daily Other Name: Elitek™
Study Arms	Experimental: Group A As Needed Rasburicase .15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed. Intervention: Drug: As Needed Rasburicase; Experimental: Group B Fixed Dose Rasburicase .15 mg/kg IV Over 30 Minutes Daily Intervention: Drug: Fixed Dose Rasburicase
Publications *	Vadhan-Raj S, Fayad LE, Fanale MA, Pro B, Rodriguez A, Hagemeister FB, Bueso-Ramos CE, Zhou X, McLaughlin PW, Fowler N, Shah J, Orlowski RZ, Samaniego F, Wang M, Cortes JE, Younes A, Kwak LW, Sarlis NJ, Romaguera JE. A randomized trial of a single-dose rasburicase versus five-daily doses in patients at risk for tumor lysis syndrome. Ann Oncol. 2012 Jun;23(6):1640-5. doi: 10.1093/annonc/mdr490. Epub 2011 Oct 19.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: May 24, 2012)	82
Original Estimated Enrollment ICMJE; (submitted: February 25, 2008)	65
Actual Study Completion Date	May 2012
Actual Primary Completion Date	May 2012 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Patients with hematological malignancies (leukemia/lymphoma) at high risk or potential risk for tumor lysis syndrome. High risk: hyperuricemia of malignancy (Uric acid levels >7.5); diagnosis of very aggressive lymphoma/leukemia based on Revised European-American Lymphoma (REAL) classification; acute myeloid leukemia, chronic myelocytic leukemia (CML) in blast crisis; high grade myelodysplastic syndrome only if they have >10% bone marrow blast involvement and given aggressive treatment similar to acute myeloid leukemia (AML) (continued on #2); (continued from # 1) Potential risk: diagnosis of aggressive lymphoma/leukemia based on (REAL) classification. Plus one or more of the following criteria: lactate dehydrogenase (LDH) >/= 2 x upper limit of normal (ULN); Stage III-IV disease; Stage I-II disease with at least 1 lymph node/tumor >5cm in diameter.; ECOG performance status 0-3; Life expectancy >3 months; Negative pregnancy test (females of child bearing potential) within </=2 weeks of rasburicase dose and use of efficient contraceptive method (both males and females). Pregnancy test may be performed on serum (HCG) or urine (HCG); Signed written informed consent (approved by the Institutional Review Board/Ethics Committee) obtained prior to study entry Exclusion Criteria: Patient receiving any investigational drug for hyperuricemia within 30 days of planned first treatment with rasburicase; Pregnancy or lactation; Known history of significant allergy problem or documented history of asthma or asthmatic bronchitis; Known history of glucose-6-phosphate dehydrogenase deficiency; Known history of hemolysis and methemoglobinemia; Previous therapy with urate oxidase; Other conditions unsuitable for participation in the trial in the Investigator's opinion; Unwillingness to comply with the requirements of the protocol; Use of allopurinol within 72 hours of the study entry
Sex/Gender	Sexes Eligible for Study: All
Ages	Child, Adult, Senior
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00628628
Other Study ID Numbers ICMJE	2006-0918
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	M.D. Anderson Cancer Center
Study Sponsor ICMJE	M.D. Anderson Cancer Center
Collaborators ICMJE	Sanofi
Investigators ICMJE	Principal Investigator: Saroj Vadhan-Raj, MD M.D. Anderson Cancer Center
PRS Account	M.D. Anderson Cancer Center
Verification Date	May 2013
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP