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

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

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.

Study Overview

• Status: Completed
• Conditions: Cancer; Hyperuricemia; Tumor Lysis Syndrome
• Intervention / Treatment: Drug: Rasburicase (SR29142); Drug: Allopurinol

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 280
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Berkeley, California, United States, 94704
      • Alta Bates Comprehensive Cancer Center
    • Los Angeles, California, United States, 90095
      • UCLA Medical Center
  • Colorado
    • Denver, Colorado, United States, 80218
      • Rocky Mountain Cancer Center
  • Florida
    • Jacksonville, Florida, United States, 32209
      • University of Florida Health Science Center at Jacksonville
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • Brooklyn, New York, United States, 11215
      • New York Methodist Hospital
    • Buffalo, New York, United States, 14263
      • Roswell Park Cancer Institute
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
    • Valhalla, New York, United States, 10595
      • New York Medical College
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97201
      • Oregon Health and Sciences University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19194
      • University of Pennsylvania Health Systems
  • Texas
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • West Virginia
    • Morgantown, West Virginia, United States, 26506-9162
      • Mary Babb Randolph Cancer Center

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. 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:

2. Eastern Cooperative Oncology Group (ECOG) performance status 0-3
3. Age >= 18 years
4. Life expectancy > 3 months
5. 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).
6. Signed written informed consent

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; Rasburicase alone given as a single agent for 5 days	Drug: Rasburicase (SR29142); 30-min IV infusion
Experimental: Arm B; 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); 30-min IV infusion; Drug: Allopurinol; Oral administration
Active Comparator: Arm C; Oral allopurinol alone given as a single agent for 5 days	Drug: Allopurinol; Oral administration

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sanofi
• Investigators: Study Director: International Clinical Development, Sanofi

Study record dates

Study Major Dates

• Study Start: April 1, 2004
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2007

Study Registration Dates

• First Submitted: September 28, 2005
• First Submitted That Met QC Criteria: September 28, 2005
• First Posted (Estimate): September 30, 2005

Study Record Updates

• Last Update Posted (Estimate): January 12, 2010
• Last Update Submitted That Met QC Criteria: January 8, 2010
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: Lymphoma; Leukemia; Hyperuricemia; Myelodysplastic Syndromes; Tumor lysis syndrome; Solid tumor cancers; Solid Tumor cancers with hyperuricemia Hyperuricemia (cancer patients only); Tumor lysis syndrome (cancer patients only)
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease; Syndrome; Tumor Lysis Syndrome; Hyperuricemia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Rasburicase; Allopurinol
• Other Study ID Numbers: EFC4978