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| Name | Class |
|---|---|
| Sanofi | INDUSTRY |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Group A | Experimental | As Needed Rasburicase .15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed. |
|
| Group B | Experimental | Fixed Dose Rasburicase .15 mg/kg IV Over 30 Minutes Daily |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| As Needed Rasburicase | Drug | .15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Plasma Uric Acid (UA) Response | 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. | First cycle of chemotherapy, up to 5 days |
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Inclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Saroj Vadhan-Raj, MD | M.D. Anderson Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UT MD Anderson Cancer Center | Houston | Texas | 77030 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22015451 | Result | 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. |
| Label | URL |
|---|---|
| MD Anderson Cancer Center | View source |
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Eighty-two patients were enrolled between February 2008 and February 2010. Two patients withdrew consent and 80 patients were randomized; 40 to the Arm A and 40 to the Arm B.
Recruitment Period: January 28, 2008 to March 8, 2010. All participants were recruited in a medical clinic setting at The UT MD Anderson Cancer Center.
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| ID | Title | Description |
|---|---|---|
| FG000 | Group A: Single Dose | As Needed Rasburicase .15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed. |
| FG001 | Group B: Daily Dose | Fixed Dose Rasburicase .15 mg/kg IV Over 30 Minutes Daily |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Group A: Single Dose | As Needed Rasburicase .15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed. |
| BG001 | Group B: Daily Dose | Fixed Dose Rasburicase .15 mg/kg IV Over 30 Minutes Daily |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Plasma Uric Acid (UA) Response | 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. | Posted | Number | participants | First cycle of chemotherapy, up to 5 days |
|
2 years, 1 month
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Group A: Single Dose | As Needed Rasburicase .15 mg/kg IV Over 30 Minutes On Day 1. Day 2-5, once daily as needed. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Leukemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Methemoglobinemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Saroj Vadhan-Raj, MD / Professor | The University of Texas (UT) MD Anderson Cancer Center | CR_Study_Registration@mdanderson.org |
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| ID | Term |
|---|---|
| D015275 | Tumor Lysis Syndrome |
| D033461 | Hyperuricemia |
| D007938 | Leukemia |
| D008223 | Lymphoma |
| D015470 | Leukemia, Myeloid, Acute |
| D015464 | Leukemia, Myelogenous, Chronic, BCR-ABL Positive |
| D009190 | Myelodysplastic Syndromes |
| ID | Term |
|---|---|
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
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| ID | Term |
|---|---|
| C469709 | rasburicase |
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| Fixed Dose Rasburicase | Drug | .15 mg/kg IV Over 30 Minutes Daily |
|
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| 0 |
| 40 |
| 40 |
| 40 |
| EG001 | Group B: Daily Dose | Fixed Dose Rasburicase .15 mg/kg IV Over 30 Minutes Daily | 2 | 40 | 40 | 40 |
| Lymphoma | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hemolysis | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Clinical tumor lysis syndrome | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Laboratory tumor lysis syndrome | Metabolism and nutrition disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hyperuricemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hyperphosphatemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hypocalcemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Hyperkalemia | Blood and lymphatic system disorders | CTCAE (3.0) | Systematic Assessment |
|
| Increased serum creatinine | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
| Renal events requiring dialysis | Renal and urinary disorders | CTCAE (3.0) | Systematic Assessment |
|
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| D007154 | Immune System Diseases |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D007951 | Leukemia, Myeloid |
| D009196 | Myeloproliferative Disorders |
| D001855 | Bone Marrow Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |