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

Phase 3

Completed

• Conditions: Tumor Lysis Syndrome; Cancer; Hyperuricemia
• Interventions: Drug: Rasburicase (SR29142); Drug: Allopurinol

• Registration Number: NCT00230178
• Lead Sponsor: Sanofi

Brief Summary

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

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 Timeline

• Study Start: 2004-04
• Study First Submitted: 2005-09-28
• Study First Submitted QC: 2005-09-28
• Study First Posted: 2005-09-30
• Primary Completion: 2007-12
• Study Completion: 2007-12
• Results First Submitted: 2009-07-22
• Results First Submitted QC: 2009-11-30
• Results First Posted: 2009-12-31
• Status Verified: 2010-01
• Last Update Submitted: 2010-01-08
• Last Update Posted: 2010-01-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 280

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

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm A	Rasburicase (SR29142)	Rasburicase alone given as a single agent for 5 days
Arm B	Rasburicase (SR29142)	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)
Arm C	Allopurinol	Oral allopurinol alone given as a single agent for 5 days
Arm B	Allopurinol	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)

Primary Outcome Measures

Name	Time	Method
Plasma Uric Acid Responder	Day 3 through Day 7	Number of patients responding to treatment defined as plasma uric acid levels at Day 3 through Day 7 \<7.5 mg/dl.

Secondary Outcome Measures

Name	Time	Method
Time to Uric Acid Control	Day 1 to Day 7	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.
Plasma Uric Acid	Day 1 to Day 7	Area under the curve concentration versus time curve extrapolated to infinity (AUC) of plasma uric acid values

Trial Locations

Locations (15)

University of Florida Health Science Center at Jacksonville; 🇺🇸 Jacksonville, Florida, United States

New York Methodist Hospital; 🇺🇸 Brooklyn, New York, United States

Rocky Mountain Cancer Center; 🇺🇸 Denver, Colorado, United States

Roswell Park Cancer Institute; 🇺🇸 Buffalo, New York, United States

Mary Babb Randolph Cancer Center; 🇺🇸 Morgantown, West Virginia, United States

University of Rochester Medical Center; 🇺🇸 Rochester, New York, United States

Alta Bates Comprehensive Cancer Center; 🇺🇸 Berkeley, California, United States

UCLA Medical Center; 🇺🇸 Los Angeles, California, United States

Ochsner Clinic Foundation; 🇺🇸 New Orleans, Louisiana, United States

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States

Oregon Health and Sciences University; 🇺🇸 Portland, Oregon, United States

University of Pennsylvania Health Systems; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Texas MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

New York Medical College; 🇺🇸 Valhalla, New York, United States