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

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

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.

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.

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.

Des-(1-6)-(7-threonine,46-threonine,291-lysine,301-serine)uricase (EC 1.7.3.3, urate oxidase) Sus scrofa (pig) tetramer, Non Acetylated, Carbamates with alpha-carboxy-omega-methoxypoly(oxyethylene), Krystexxa, Methoxypolyethylene Glycol Uricase, Oxidase, Urate (Synthetic Sus scrofa variant pigks-DN subunit), homotetramer, amide with alpha-carboxy-omega-methoxypoly(oxy-1,2-ethanediyl), Polyethylene Glycol-uricase, Puricase

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.

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.

Will examine the association of baseline characteristics with serum uric acid level using the Fisher's exact test, student's t-test, paired t-test, Wilcoxon rank-sum test, or Wilcoxon signed-rank test and will employ graphical methods when useful.

Inclusion 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 (measured as average of 3 days prior, +/- 1 days) High risk for tumor lysis syndrome based on the MD Anderson Tumor Lysis Syndrome (TLS) risk score Exclusion Criteria: 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) Has received rasburicase during current admission.