Pegloticase for the Reduction of Uric Acid in Patients With Tumor Lysis Syndrome

Study Overview
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Brief Summary
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This trial studies the effect of pegloticase in reducing uric acid levels in patients with hyperuricemia (high blood levels of uric acid) caused by tumor lysis syndrome. Tumor lysis syndrome occurs when the breakdown products of cancer cells, such as uric acid, enter the blood stream. High levels of uric acid in blood may cause kidney damage and reduce kidney function. The goal of this trial is to learn if pegloticase may lower uric acid levels in blood when given to cancer patients with hyperuricemia caused by tumor lysis syndrome.

Detailed Description
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PRIMARY OBJECTIVE: I. To collect preliminary data on the effectiveness of a single dose of pegloticase in lowering serum uric acid levels to less than 6.0 mg/dl within 24 hours in patients with hyperuricemia in the setting of tumor lysis syndrome. SECONDARY OBJECTIVES: I. To assess the effect of pegloticase on renal function in patients with hyperuricemia in the setting of tumor lysis syndrome as measured by changes in serum creatinine/estimated glomerular filtration rate (eGFR) and urine output. II. To estimate the rate of renal replacement therapy initiation for acute kidney injury secondary to tumor lysis syndrome among patients treated with pegloticase. OUTLINE: Patients receive pegloticase intravenously (IV) over 120 minutes. Patients whose serum uric acid does not drop below 6 mg/dL within 24 hours receive a second dose of pegloticase IV over 120 minutes on day 2. Patients whose serum uric acid does not drop below 6 mg/dL after two doses of pegloticase receive standard of care rasburicase IV once daily (QD) for 5 days.

Official Title
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Effect of Pegloticase on Reduction of Uric Acid in Patients With Tumor Lysis Syndrome: A Pilot Pragmatic Clinical Trial

Conditions
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Hematopoietic and Lymphoid Cell Neoplasm, Malignant Solid Neoplasm, Tumor Lysis Syndrome

Intervention / Treatment
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* Drug: Pegloticase
* Drug: Rasburicase


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For inclusion in the study, patients should fulfill the following criteria: Signed informed consent prior to any study specific procedures (patient or caregiver) Male or female 18 years of age or older In the investigator's opinion, expected survival of at least 1 month Deemed stable by the investigator Serum Uric Acid ≥ 6 mg/dL Risk for tumor lysis syndrome based on the MD Anderson TLS risk score Exclusion Criteria: Patients will be ineligible for study enrollment if any of the following exclusion criteria are fulfilled: Inability or refusal to give informed consent (patient or caregiver) Subject unwilling to take study medication Known allergy to uricase Pregnant Breastfeeding Known glucose-6-phosphate dehydrogenase (G6PD) deficiency Transfusion in last 7 days (as this interferes with G6PD test), with the exception of platelet transfusions. Has received rasburicase during current admission.(Can be considered if >4 days after last Rasburicase administered, current or previous admission)

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: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment (pegloticase)<br>Patients receive pegloticase IV over 120 minutes. Patients whose serum uric acid does not drop below 6 mg/dL within 24 hours receive a second dose of pegloticase IV over 120 minutes on day 2. Patients whose serum uric acid does not drop below 6 mg/dL after two doses of pegloticase receive standard of care rasburicase IV QD for 5 days. | Drug: Pegloticase<br>* Given IV<br>* Other names: Puricase;Drug: Rasburicase<br>* Given IV<br>* Other names: Urate Oxidase;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate | Will estimate the 24-hour response rate along with the corresponding 90% confidence interval. In addition, the report will present plots of uric acid levels across all time points. | Within 24 hours of single dose of pegloticase | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time from pegloticase infusion until serum uric acid levels drop to 6 mg/dL | Will display results in frequency tables and plots of serum uric acid levels across time. | Up to 14 days after pegloticase administration | 
| Renal function | Will summarize serum creatinine and estimated glomerular filtration rate at each time point and plot these lab values across time. Finally, will calculate the rate and 90% confidence interval for the initiation of renal replacement therapy within the 14-day observation window. | Up to 14 days after pegloticase administration |