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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hematopoietic and Lymphoid Cell Neoplasm; Malignant Solid Neoplasm; Tumor Lysis Syndrome
• Intervention / Treatment: Drug: Pegloticase; Drug: Rasburicase

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sreedhar Mandayam, MD; Phone Number: 713-745-8597; Email: samandayam@mdanderson.org

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

For inclusion in the study, patients should fulfill the following criteria:

1. Signed informed consent prior to any study specific procedures (patient or caregiver)
2. Male or female 18 years of age or older
3. In the investigator's opinion, expected survival of at least 1 month
4. Deemed stable by the investigator
5. Serum Uric Acid ≥ 6 mg/dL
6. 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:

1. Inability or refusal to give informed consent (patient or caregiver)
2. Subject unwilling to take study medication
3. Known allergy to uricase
4. Pregnant
5. Breastfeeding
6. Known glucose-6-phosphate dehydrogenase (G6PD) deficiency
7. Transfusion in last 7 days (as this interferes with G6PD test), with the exception of platelet transfusions.
8. Has received rasburicase during current admission.(Can be considered if >4 days after last Rasburicase administered, current or previous admission)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (pegloticase); 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; Given IV; Other Names: 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; Drug: Rasburicase; Given IV; Other Names: Elitek; Recombinant Urate Oxidase; SR 29142; SR-29142; Urate Oxidase

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum uric acid level	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.	Up to 14 days after pegloticase administration

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Investigators: Principal Investigator: Sreedhar Mandayam, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• M D Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): April 5, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: February 3, 2021
• First Submitted That Met QC Criteria: February 4, 2021
• First Posted (Actual): February 9, 2021

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease; Neoplasms; Syndrome; Tumor Lysis Syndrome; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Protective Agents; Antioxidants; Gout Suppressants; Rasburicase; Uric Acid
• Other Study ID Numbers: 2020-0330 (Other Identifier: M D Anderson Cancer Center); NCI-2020-13890 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No