Rasburicase Versus Allopurinol in Tumor Patients at Risk for Hyperuricemia and Tumor Lysis Syndrome

Study Overview
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Brief Summary
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This is a randomized, multi-center, open-label, parallel group study with three arms: Rasburicase alone Rasburicase followed by Allopurinol Allopurinol alone The primary objective is to compare the adequacy of control of plasma uric acid concentration and the safety profile among the three arms.

Detailed Description
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After signing the informed consent and having met the inclusion criteria, patients will be randomized to 1 of the 3 arms and treated for a total duration of 5 days. Patients in all arms will receive chemotherapy beginning 4-24 hours after the first dose of rasburicase or allopurinol.

Official Title
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Evaluation of Single Agent Rasburicase for 5 Days Versus Sequential Treatment With Rasburicase From Day 1 Through 3 Followed by Oral Allopurinol From Day 3 Through 5 (Overlap on Day 3) Versus Single Agent Oral Allopurinol for 5 Days in the Management of Plasma Uric Acid in Adult Patients With Leukemia, Lymphoma, and Solid Tumor Malignancies at Risk for Hyperuricemia and Tumor Lysis Syndrome

Conditions
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Cancer, Tumor Lysis Syndrome, Hyperuricemia

Intervention / Treatment
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* Drug: Rasburicase (SR29142)
* Drug: Allopurinol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meets high risk or at potential risk for tumor lysis syndrome (TLS): A patient is at high risk for TLS if he/she presents with: Hyperuricemia of malignancy (plasma uric acid > 7.5 mg/dL); A diagnosis of very aggressive lymphoma/leukemia based on the Revised European-American Lymphoma (REAL) classification of lymphoma/leukemia; Acute myeloid leukemia (AML); Chronic myeloid leukemia (CML) in blast crisis; or High grade myelodysplastic syndrome (refractory anemia with excess blast, chronic myelomonocytic leukemia, and refractory anemia with excess blast in transformation) only if they have > 10% bone marrow blast involvement and are given aggressive treatment similar to AML. A patient is at potential risk for TLS if he/she presents with: A diagnosis of aggressive lymphoma/leukemia based on the REAL classification of lymphoma/leukemia plus 1 or more of the following criteria: Lactate dehydrogenase (LDH) >= 2 x upper limit of normal (ULN) (IU/L) Stage III-IV disease Stage I-II disease with at least 1 lymph node/tumor > 5 cm in diameter In addition to the above-mentioned eligibility criteria, the patients should have the following criteria: Eastern Cooperative Oncology Group (ECOG) performance status 0-3 Age >= 18 years Life expectancy > 3 months Negative pregnancy test (females of child bearing potential) and use of effective contraceptive method (for both males and females). A pregnancy test may be performed on serum or urine human chorionic gonadotropin (HCG). Signed written informed consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A<br>Rasburicase alone given as a single agent for 5 days | Drug: Rasburicase (SR29142)<br>* 30-min IV infusion<br>|
| Experimental: Arm B<br>Rasburicase alone given as a single agent from Day 1 through Day 3, followed by oral allopurinol given from Day 3 through Day 5 (Day 3 is an overlap) | Drug: Rasburicase (SR29142)<br>* 30-min IV infusion<br>Drug: Allopurinol<br>* Oral administration<br>|
| Active Comparator: Arm C<br>Oral allopurinol alone given as a single agent for 5 days | Drug: Allopurinol<br>* Oral administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Uric Acid Responder | Number of patients responding to treatment defined as plasma uric acid levels at Day 3 through Day 7 <7.5 mg/dl. | Day 3 through Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Uric Acid | Area under the curve concentration versus time curve extrapolated to infinity (AUC) of plasma uric acid values | Day 1 to Day 7 | 
| Time to Uric Acid Control | Time from the first dose of study drug to the time at which plasma uric acid concentrations were determined <=7.5 mg/dl, measured -4, 4, 24, 48, 72, 96, 120, and 144 hours after infusion. | Day 1 to Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperuricemia, Tumor lysis syndrome, Leukemia, Lymphoma, Myelodysplastic Syndromes, Solid tumor cancers, Solid Tumor cancers with hyperuricemia Hyperuricemia (cancer patients only), Tumor lysis syndrome (cancer patients only)